                         SEQUENCE LISTING

<110>  City of Hope
 
<120>  COMPOSITIONS AND USES OF CD19 TARGETED CHIMERIC ANTIGEN RECEPTOR 
       MODIFIED IMMUNE CELLS

<130>  40056-0060WO1

<140>  PCT/US2021/062708
<141>  2021-12-09

<150>  US 63/123,433
<151>  2020-12-09

<160>  61    

<170>  PatentIn version 3.5

<210>  1
<211>  245
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv VH4Vk1

<400>  1

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Gln Val Gln 
        115                 120                 125             


Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Thr Leu Ser 
    130                 135                 140                 


Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Ile Gly Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Val 
            180                 185                 190         


Thr Ile Ser Val Asp Asn Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser 
        195                 200                 205             


Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser 
                245 


<210>  2
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  linker

<400>  2

Gly Gly Gly Ser Ser Gly Gly Gly Ser Gly 
1               5                   10  


<210>  3
<211>  12
<212>  PRT
<213>  Artificial

<220>
<223>  IgG4 hinge (S-->P) (S228P)

<400>  3

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 
1               5                   10          


<210>  4
<211>  12
<212>  PRT
<213>  Homo sapiens

<400>  4

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro 
1               5                   10          


<210>  5
<211>  22
<212>  PRT
<213>  Artificial

<220>
<223>  IgG4 hinge (S228P)+ linker

<400>  5

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Gly Gly Gly Ser 
1               5                   10                  15      


Ser Gly Gly Gly Ser Gly 
            20          


<210>  6
<211>  39
<212>  PRT
<213>  Homo sapiens

<400>  6

Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn 
1               5                   10                  15      


Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu 
            20                  25                  30          


Phe Pro Gly Pro Ser Lys Pro 
        35                  


<210>  7
<211>  48
<212>  PRT
<213>  Homo sapiens

<400>  7

Ala Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro 
1               5                   10                  15      


Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro 
            20                  25                  30          


Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp 
        35                  40                  45              


<210>  8
<211>  45
<212>  PRT
<213>  Homo sapiens

<400>  8

Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala 
1               5                   10                  15      


Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly 
            20                  25                  30          


Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp 
        35                  40                  45  


<210>  9
<211>  129
<212>  PRT
<213>  Artificial

<220>
<223>  IgG4 (HL-CH3) (includes S228P in hinge)

<400>  9

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Gly Gly Gly Ser 
1               5                   10                  15      


Ser Gly Gly Gly Ser Gly Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            20                  25                  30          


Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        35                  40                  45              


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    50                  55                  60                  


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
65                  70                  75                  80  


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 
                85                  90                  95      


Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            100                 105                 110         


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 
        115                 120                 125             


Lys 
    


<210>  10
<211>  229
<212>  PRT
<213>  Artificial

<220>
<223>  IgG4 (L235E, N297Q)

<400>  10

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe 
1               5                   10                  15      


Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              


Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Gln Ser 
65                  70                  75                  80  


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         


Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             


Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 
            180                 185                 190         


Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 


Leu Ser Leu Gly Lys 
225                 


<210>  11
<211>  229
<212>  PRT
<213>  Artificial

<220>
<223>  IgG4 (S228P, L235E, N297Q)

<400>  11

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe 
1               5                   10                  15      


Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              


Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Gln Ser 
65                  70                  75                  80  


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         


Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             


Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 
            180                 185                 190         


Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 


Leu Ser Leu Gly Lys 
225                 


<210>  12
<211>  107
<212>  PRT
<213>  Homo sapiens

<400>  12

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu 
1               5                   10                  15      


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
            20                  25                  30          


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
        35                  40                  45              


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
    50                  55                  60                  


Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 
65                  70                  75                  80  


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                85                  90                  95      


Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
            100                 105         


<210>  13
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  13

Leu Cys Tyr Leu Leu Asp Gly Ile Leu Phe Ile Tyr Gly Val Ile Leu 
1               5                   10                  15      


Thr Ala Leu Phe Leu 
            20      


<210>  14
<211>  27
<212>  PRT
<213>  Homo sapiens

<400>  14

Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 
1               5                   10                  15      


Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 
            20                  25          


<210>  15
<211>  28
<212>  PRT
<213>  Homo sapiens

<400>  15

Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser 
1               5                   10                  15      


Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 
            20                  25              


<210>  16
<211>  22
<212>  PRT
<213>  Homo sapiens

<400>  16

Met Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile 
1               5                   10                  15      


Gly Leu Gly Ile Phe Phe 
            20          


<210>  17
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  17

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 
1               5                   10                  15      


Ser Leu Val Ile Thr 
            20      


<210>  18
<211>  23
<212>  PRT
<213>  Homo sapiens

<400>  18

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 
1               5                   10                  15      


Ser Leu Val Ile Thr Leu Tyr 
            20              


<210>  19
<211>  24
<212>  PRT
<213>  Homo sapiens

<400>  19

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 
1               5                   10                  15      


Ser Leu Val Ile Thr Leu Tyr Cys 
            20                  


<210>  20
<211>  27
<212>  PRT
<213>  Homo sapiens

<400>  20

Ile Ile Ser Phe Phe Leu Ala Leu Thr Ser Thr Ala Leu Leu Phe Leu 
1               5                   10                  15      


Leu Phe Phe Leu Thr Leu Arg Phe Ser Val Val 
            20                  25          


<210>  21
<211>  112
<212>  PRT
<213>  Homo sapiens

<400>  21

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 
1               5                   10                  15      


Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 
            20                  25                  30          


Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 
        35                  40                  45              


Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 
    50                  55                  60                  


Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 
65                  70                  75                  80  


Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 
                85                  90                  95      


Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
            100                 105                 110         


<210>  22
<211>  41
<212>  PRT
<213>  Homo sapiens

<400>  22

Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr 
1               5                   10                  15      


Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro 
            20                  25                  30          


Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
        35                  40      


<210>  23
<211>  41
<212>  PRT
<213>  Artificial

<220>
<223>  CD28gg

<400>  23

Arg Ser Lys Arg Ser Arg Gly Gly His Ser Asp Tyr Met Asn Met Thr 
1               5                   10                  15      


Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro 
            20                  25                  30          


Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
        35                  40      


<210>  24
<211>  42
<212>  PRT
<213>  Homo sapiens

<400>  24

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met 
1               5                   10                  15      


Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe 
            20                  25                  30          


Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
        35                  40          


<210>  25
<211>  42
<212>  PRT
<213>  Homo sapiens

<400>  25

Ala Leu Tyr Leu Leu Arg Arg Asp Gln Arg Leu Pro Pro Asp Ala His 
1               5                   10                  15      


Lys Pro Pro Gly Gly Gly Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln 
            20                  25                  30          


Ala Asp Ala His Ser Thr Leu Ala Lys Ile 
        35                  40          


<210>  26
<211>  323
<212>  PRT
<213>  Homo sapiens

<400>  26

Met Pro Pro Pro Arg Leu Leu Phe Phe Leu Leu Phe Leu Thr Pro Met 
1               5                   10                  15      


Glu Val Arg Pro Glu Glu Pro Leu Val Val Lys Val Glu Glu Gly Asp 
            20                  25                  30          


Asn Ala Val Leu Gln Cys Leu Lys Gly Thr Ser Asp Gly Pro Thr Gln 
        35                  40                  45              


Gln Leu Thr Trp Ser Arg Glu Ser Pro Leu Lys Pro Phe Leu Lys Leu 
    50                  55                  60                  


Ser Leu Gly Leu Pro Gly Leu Gly Ile His Met Arg Pro Leu Ala Ile 
65                  70                  75                  80  


Trp Leu Phe Ile Phe Asn Val Ser Gln Gln Met Gly Gly Phe Tyr Leu 
                85                  90                  95      


Cys Gln Pro Gly Pro Pro Ser Glu Lys Ala Trp Gln Pro Gly Trp Thr 
            100                 105                 110         


Val Asn Val Glu Gly Ser Gly Glu Leu Phe Arg Trp Asn Val Ser Asp 
        115                 120                 125             


Leu Gly Gly Leu Gly Cys Gly Leu Lys Asn Arg Ser Ser Glu Gly Pro 
    130                 135                 140                 


Ser Ser Pro Ser Gly Lys Leu Met Ser Pro Lys Leu Tyr Val Trp Ala 
145                 150                 155                 160 


Lys Asp Arg Pro Glu Ile Trp Glu Gly Glu Pro Pro Cys Val Pro Pro 
                165                 170                 175     


Arg Asp Ser Leu Asn Gln Ser Leu Ser Gln Asp Leu Thr Met Ala Pro 
            180                 185                 190         


Gly Ser Thr Leu Trp Leu Ser Cys Gly Val Pro Pro Asp Ser Val Ser 
        195                 200                 205             


Arg Gly Pro Leu Ser Trp Thr His Val His Pro Lys Gly Pro Lys Ser 
    210                 215                 220                 


Leu Leu Ser Leu Glu Leu Lys Asp Asp Arg Pro Ala Arg Asp Met Trp 
225                 230                 235                 240 


Val Met Glu Thr Gly Leu Leu Leu Pro Arg Ala Thr Ala Gln Asp Ala 
                245                 250                 255     


Gly Lys Tyr Tyr Cys His Arg Gly Asn Leu Thr Met Ser Phe His Leu 
            260                 265                 270         


Glu Ile Thr Ala Arg Pro Val Leu Trp His Trp Leu Leu Arg Thr Gly 
        275                 280                 285             


Gly Trp Lys Val Ser Ala Val Thr Leu Ala Tyr Leu Ile Phe Cys Leu 
    290                 295                 300                 


Cys Ser Leu Val Gly Ile Leu His Leu Gln Arg Ala Leu Val Leu Arg 
305                 310                 315                 320 


Arg Lys Arg 
            


<210>  27
<211>  24
<212>  PRT
<213>  Homo sapiens

<400>  27

Leu Glu Gly Gly Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp 
1               5                   10                  15      


Val Glu Glu Asn Pro Gly Pro Arg 
            20                  


<210>  28
<211>  354
<212>  PRT
<213>  Homo sapiens

<400>  28

Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro Ala Phe Leu 
1               5                   10                  15      


Leu Ile Pro Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys 
            20                  25                  30          


Asp Ser Leu Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys 
        35                  40                  45              


Thr Ser Ile Ser Gly Asp Leu His Ile Leu Pro Val Ala Phe Arg Gly 
    50                  55                  60                  


Asp Ser Phe Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile 
65                  70                  75                  80  


Leu Lys Thr Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp 
                85                  90                  95      


Pro Glu Asn Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile 
            100                 105                 110         


Arg Gly Arg Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val Ser 
        115                 120                 125             


Leu Asn Ile Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp 
    130                 135                 140                 


Gly Asp Val Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr 
145                 150                 155                 160 


Ile Asn Trp Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile 
                165                 170                 175     


Ile Ser Asn Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys 
            180                 185                 190         


His Ala Leu Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp 
        195                 200                 205             


Cys Val Ser Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys 
    210                 215                 220                 


Cys Asn Leu Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu 
225                 230                 235                 240 


Cys Ile Gln Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr 
                245                 250                 255     


Cys Thr Gly Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile 
            260                 265                 270         


Asp Gly Pro His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu 
        275                 280                 285             


Asn Asn Thr Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His 
    290                 295                 300                 


Leu Cys His Pro Asn Cys Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu 
305                 310                 315                 320 


Gly Cys Pro Thr Asn Gly Pro Lys Ile Pro Ser Ile Ala Thr Gly Met 
                325                 330                 335     


Val Gly Ala Leu Leu Leu Leu Leu Val Val Ala Leu Gly Ile Gly Leu 
            340                 345                 350         


Phe Met 
        


<210>  29
<211>  575
<212>  PRT
<213>  Artificial

<220>
<223>  VH4Vk1-IgG4 - CD4TM-41BB with signal sequence

<400>  29

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
        35                  40                  45              


Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Gln Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
        115                 120                 125             


Lys Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 
    130                 135                 140                 


Thr Lys Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Ala 
145                 150                 155                 160 


Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu 
                165                 170                 175     


Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu 
            180                 185                 190         


Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser 
        195                 200                 205             


Ala Leu Lys Ser Arg Val Thr Ile Ser Val Asp Asn Ser Lys Asn Gln 
    210                 215                 220                 


Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
                245                 250                 255     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Ser Lys Tyr Gly 
            260                 265                 270         


Pro Pro Cys Pro Pro Cys Pro Gly Gly Gly Ser Ser Gly Gly Gly Ser 
        275                 280                 285             


Gly Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln 
    290                 295                 300                 


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
305                 310                 315                 320 


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
                325                 330                 335     


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
            340                 345                 350         


Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu 
        355                 360                 365             


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
    370                 375                 380                 


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Met Ala Leu Ile 
385                 390                 395                 400 


Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile 
                405                 410                 415     


Phe Phe Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro 
            420                 425                 430         


Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys 
        435                 440                 445             


Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Gly Gly Gly Arg 
    450                 455                 460                 


Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln 
465                 470                 475                 480 


Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp 
                485                 490                 495     


Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro 
            500                 505                 510         


Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp 
        515                 520                 525             


Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg 
    530                 535                 540                 


Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr 
545                 550                 555                 560 


Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
                565                 570                 575 


<210>  30
<211>  575
<212>  PRT
<213>  Artificial

<220>
<223>  4D5-IgG4 - CD4TM-41BB with signal sequence

<400>  30

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
        35                  40                  45              


Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
        115                 120                 125             


Lys Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 
    130                 135                 140                 


Thr Lys Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 
145                 150                 155                 160 


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Ser Leu 
                165                 170                 175     


Pro Asp Tyr Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
            180                 185                 190         


Glu Trp Val Ala Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp 
        195                 200                 205             


Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr 
    210                 215                 220                 


Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ser Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
                245                 250                 255     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Ser Lys Tyr Gly 
            260                 265                 270         


Pro Pro Cys Pro Pro Cys Pro Gly Gly Gly Ser Ser Gly Gly Gly Ser 
        275                 280                 285             


Gly Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln 
    290                 295                 300                 


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
305                 310                 315                 320 


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
                325                 330                 335     


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
            340                 345                 350         


Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu 
        355                 360                 365             


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
    370                 375                 380                 


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Met Ala Leu Ile 
385                 390                 395                 400 


Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile 
                405                 410                 415     


Phe Phe Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro 
            420                 425                 430         


Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys 
        435                 440                 445             


Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Gly Gly Gly Arg 
    450                 455                 460                 


Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln 
465                 470                 475                 480 


Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp 
                485                 490                 495     


Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro 
            500                 505                 510         


Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp 
        515                 520                 525             


Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg 
    530                 535                 540                 


Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr 
545                 550                 555                 560 


Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
                565                 570                 575 


<210>  31
<211>  553
<212>  PRT
<213>  Artificial

<220>
<223>  VH4Vk1-IgG4 - CD4TM-41BB

<400>  31

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Gln Val Gln 
        115                 120                 125             


Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Thr Leu Ser 
    130                 135                 140                 


Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Ile Gly Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Val 
            180                 185                 190         


Thr Ile Ser Val Asp Asn Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser 
        195                 200                 205             


Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys 
                245                 250                 255     


Pro Gly Gly Gly Ser Ser Gly Gly Gly Ser Gly Gly Gln Pro Arg Glu 
            260                 265                 270         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
        275                 280                 285             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    290                 295                 300                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
305                 310                 315                 320 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
                325                 330                 335     


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
            340                 345                 350         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        355                 360                 365             


Ser Leu Ser Leu Gly Lys Met Ala Leu Ile Val Leu Gly Gly Val Ala 
    370                 375                 380                 


Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile Phe Phe Lys Arg Gly Arg 
385                 390                 395                 400 


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
                405                 410                 415     


Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu 
            420                 425                 430         


Glu Gly Gly Cys Glu Leu Gly Gly Gly Arg Val Lys Phe Ser Arg Ser 
        435                 440                 445             


Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu 
    450                 455                 460                 


Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg 
465                 470                 475                 480 


Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln 
                485                 490                 495     


Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr 
            500                 505                 510         


Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp 
        515                 520                 525             


Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala 
    530                 535                 540                 


Leu His Met Gln Ala Leu Pro Pro Arg 
545                 550             


<210>  32
<211>  245
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv 4D5

<400>  32

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Gln 
        115                 120                 125             


Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
    130                 135                 140                 


Leu Ser Cys Ala Ala Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
            180                 185                 190         


Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn 
        195                 200                 205             


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ser Arg His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser 
                245 


<210>  33
<211>  553
<212>  PRT
<213>  Artificial

<220>
<223>  4D5-IgG4 - CD4TM-41BB

<400>  33

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Gln 
        115                 120                 125             


Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
    130                 135                 140                 


Leu Ser Cys Ala Ala Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
            180                 185                 190         


Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn 
        195                 200                 205             


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ser Arg His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys 
                245                 250                 255     


Pro Gly Gly Gly Ser Ser Gly Gly Gly Ser Gly Gly Gln Pro Arg Glu 
            260                 265                 270         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
        275                 280                 285             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    290                 295                 300                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
305                 310                 315                 320 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
                325                 330                 335     


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
            340                 345                 350         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        355                 360                 365             


Ser Leu Ser Leu Gly Lys Met Ala Leu Ile Val Leu Gly Gly Val Ala 
    370                 375                 380                 


Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile Phe Phe Lys Arg Gly Arg 
385                 390                 395                 400 


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
                405                 410                 415     


Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu 
            420                 425                 430         


Glu Gly Gly Cys Glu Leu Gly Gly Gly Arg Val Lys Phe Ser Arg Ser 
        435                 440                 445             


Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu 
    450                 455                 460                 


Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg 
465                 470                 475                 480 


Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln 
                485                 490                 495     


Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr 
            500                 505                 510         


Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp 
        515                 520                 525             


Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala 
    530                 535                 540                 


Leu His Met Gln Ala Leu Pro Pro Arg 
545                 550             


<210>  34
<211>  4
<212>  PRT
<213>  Artificial

<220>
<223>  linker

<400>  34

Gly Gly Gly Ser 
1               


<210>  35
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  linker

<400>  35

Gly Gly Gly Gly Ser 
1               5   


<210>  36
<211>  22
<212>  PRT
<213>  Homo sapiens

<400>  36

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  37
<211>  531
<212>  PRT
<213>  Artificial

<220>
<223>  VH4Vk1-IgG4 - CD4TM-41BB

<400>  37

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Gln Val Gln 
        115                 120                 125             


Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Thr Leu Ser 
    130                 135                 140                 


Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Ile Gly Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Val 
            180                 185                 190         


Thr Ile Ser Val Asp Asn Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser 
        195                 200                 205             


Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
                245                 250                 255     


Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
            260                 265                 270         


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
        275                 280                 285             


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
    290                 295                 300                 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
305                 310                 315                 320 


Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                325                 330                 335     


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
            340                 345                 350         


Met Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile 
        355                 360                 365             


Gly Leu Gly Ile Phe Phe Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile 
    370                 375                 380                 


Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp 
385                 390                 395                 400 


Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
                405                 410                 415     


Gly Gly Gly Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr 
            420                 425                 430         


Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg 
        435                 440                 445             


Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met 
    450                 455                 460                 


Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu 
465                 470                 475                 480 


Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys 
                485                 490                 495     


Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu 
            500                 505                 510         


Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu 
        515                 520                 525             


Pro Pro Arg 
    530     


<210>  38
<211>  553
<212>  PRT
<213>  Artificial

<220>
<223>  VH4Vk1-IgG4 - CD4TM-41BB with signal sequence

<400>  38

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
        35                  40                  45              


Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Gln Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
        115                 120                 125             


Lys Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 
    130                 135                 140                 


Thr Lys Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Ala 
145                 150                 155                 160 


Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu 
                165                 170                 175     


Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu 
            180                 185                 190         


Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser 
        195                 200                 205             


Ala Leu Lys Ser Arg Val Thr Ile Ser Val Asp Asn Ser Lys Asn Gln 
    210                 215                 220                 


Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
                245                 250                 255     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu 
            260                 265                 270         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
        275                 280                 285             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    290                 295                 300                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
305                 310                 315                 320 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
                325                 330                 335     


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
            340                 345                 350         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        355                 360                 365             


Ser Leu Ser Leu Gly Lys Met Ala Leu Ile Val Leu Gly Gly Val Ala 
    370                 375                 380                 


Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile Phe Phe Lys Arg Gly Arg 
385                 390                 395                 400 


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
                405                 410                 415     


Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu 
            420                 425                 430         


Glu Gly Gly Cys Glu Leu Gly Gly Gly Arg Val Lys Phe Ser Arg Ser 
        435                 440                 445             


Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu 
    450                 455                 460                 


Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg 
465                 470                 475                 480 


Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln 
                485                 490                 495     


Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr 
            500                 505                 510         


Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp 
        515                 520                 525             


Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala 
    530                 535                 540                 


Leu His Met Gln Ala Leu Pro Pro Arg 
545                 550             


<210>  39
<211>  531
<212>  PRT
<213>  Artificial

<220>
<223>  4D5-IgG4 - CD4TM-41BB

<400>  39

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Gln 
        115                 120                 125             


Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
    130                 135                 140                 


Leu Ser Cys Ala Ala Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
            180                 185                 190         


Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn 
        195                 200                 205             


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ser Arg His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
                245                 250                 255     


Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
            260                 265                 270         


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
        275                 280                 285             


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
    290                 295                 300                 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
305                 310                 315                 320 


Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                325                 330                 335     


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
            340                 345                 350         


Met Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile 
        355                 360                 365             


Gly Leu Gly Ile Phe Phe Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile 
    370                 375                 380                 


Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp 
385                 390                 395                 400 


Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
                405                 410                 415     


Gly Gly Gly Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr 
            420                 425                 430         


Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg 
        435                 440                 445             


Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met 
    450                 455                 460                 


Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu 
465                 470                 475                 480 


Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys 
                485                 490                 495     


Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu 
            500                 505                 510         


Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu 
        515                 520                 525             


Pro Pro Arg 
    530     


<210>  40
<211>  553
<212>  PRT
<213>  Artificial

<220>
<223>  4D5-IgG4 - CD4TM-41BB with signal sequence

<400>  40

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
        35                  40                  45              


Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
        115                 120                 125             


Lys Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 
    130                 135                 140                 


Thr Lys Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 
145                 150                 155                 160 


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Ser Leu 
                165                 170                 175     


Pro Asp Tyr Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
            180                 185                 190         


Glu Trp Val Ala Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp 
        195                 200                 205             


Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr 
    210                 215                 220                 


Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ser Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
                245                 250                 255     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu 
            260                 265                 270         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
        275                 280                 285             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    290                 295                 300                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
305                 310                 315                 320 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
                325                 330                 335     


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
            340                 345                 350         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        355                 360                 365             


Ser Leu Ser Leu Gly Lys Met Ala Leu Ile Val Leu Gly Gly Val Ala 
    370                 375                 380                 


Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile Phe Phe Lys Arg Gly Arg 
385                 390                 395                 400 


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
                405                 410                 415     


Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu 
            420                 425                 430         


Glu Gly Gly Cys Glu Leu Gly Gly Gly Arg Val Lys Phe Ser Arg Ser 
        435                 440                 445             


Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu 
    450                 455                 460                 


Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg 
465                 470                 475                 480 


Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln 
                485                 490                 495     


Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr 
            500                 505                 510         


Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp 
        515                 520                 525             


Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala 
    530                 535                 540                 


Leu His Met Gln Ala Leu Pro Pro Arg 
545                 550             


<210>  41
<211>  552
<212>  PRT
<213>  Artificial

<220>
<223>  VH4Vk1-IgG4 - CD8TM-41BB

<400>  41

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Gln Val Gln 
        115                 120                 125             


Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Thr Leu Ser 
    130                 135                 140                 


Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Ile Gly Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Val 
            180                 185                 190         


Thr Ile Ser Val Asp Asn Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser 
        195                 200                 205             


Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys 
                245                 250                 255     


Pro Gly Gly Gly Ser Ser Gly Gly Gly Ser Gly Gly Gln Pro Arg Glu 
            260                 265                 270         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
        275                 280                 285             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    290                 295                 300                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
305                 310                 315                 320 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
                325                 330                 335     


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
            340                 345                 350         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        355                 360                 365             


Ser Leu Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr 
    370                 375                 380                 


Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Lys Arg Gly Arg Lys 
385                 390                 395                 400 


Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr 
                405                 410                 415     


Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu 
            420                 425                 430         


Gly Gly Cys Glu Leu Gly Gly Gly Arg Val Lys Phe Ser Arg Ser Ala 
        435                 440                 445             


Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu 
    450                 455                 460                 


Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly 
465                 470                 475                 480 


Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu 
                485                 490                 495     


Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser 
            500                 505                 510         


Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly 
        515                 520                 525             


Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu 
    530                 535                 540                 


His Met Gln Ala Leu Pro Pro Arg 
545                 550         


<210>  42
<211>  574
<212>  PRT
<213>  Artificial

<220>
<223>  VH4Vk1-IgG4 - CD8TM-41BB with signal sequence

<400>  42

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
        35                  40                  45              


Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Gln Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
        115                 120                 125             


Lys Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 
    130                 135                 140                 


Thr Lys Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Ala 
145                 150                 155                 160 


Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu 
                165                 170                 175     


Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu 
            180                 185                 190         


Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser 
        195                 200                 205             


Ala Leu Lys Ser Arg Val Thr Ile Ser Val Asp Asn Ser Lys Asn Gln 
    210                 215                 220                 


Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
                245                 250                 255     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Ser Lys Tyr Gly 
            260                 265                 270         


Pro Pro Cys Pro Pro Cys Pro Gly Gly Gly Ser Ser Gly Gly Gly Ser 
        275                 280                 285             


Gly Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln 
    290                 295                 300                 


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
305                 310                 315                 320 


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
                325                 330                 335     


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
            340                 345                 350         


Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu 
        355                 360                 365             


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
    370                 375                 380                 


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ile Tyr Ile Trp 
385                 390                 395                 400 


Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile 
                405                 410                 415     


Thr Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe 
            420                 425                 430         


Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg 
        435                 440                 445             


Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Gly Gly Gly Arg Val 
    450                 455                 460                 


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn 
465                 470                 475                 480 


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
                485                 490                 495     


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
            500                 505                 510         


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
        515                 520                 525             


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
    530                 535                 540                 


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
545                 550                 555                 560 


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
                565                 570                 


<210>  43
<211>  552
<212>  PRT
<213>  Artificial

<220>
<223>  4D5-IgG4 - CD8TM-41BB

<400>  43

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Gln 
        115                 120                 125             


Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
    130                 135                 140                 


Leu Ser Cys Ala Ala Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
            180                 185                 190         


Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn 
        195                 200                 205             


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ser Arg His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys 
                245                 250                 255     


Pro Gly Gly Gly Ser Ser Gly Gly Gly Ser Gly Gly Gln Pro Arg Glu 
            260                 265                 270         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
        275                 280                 285             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    290                 295                 300                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
305                 310                 315                 320 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
                325                 330                 335     


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
            340                 345                 350         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        355                 360                 365             


Ser Leu Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr 
    370                 375                 380                 


Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Lys Arg Gly Arg Lys 
385                 390                 395                 400 


Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr 
                405                 410                 415     


Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu 
            420                 425                 430         


Gly Gly Cys Glu Leu Gly Gly Gly Arg Val Lys Phe Ser Arg Ser Ala 
        435                 440                 445             


Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu 
    450                 455                 460                 


Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly 
465                 470                 475                 480 


Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu 
                485                 490                 495     


Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser 
            500                 505                 510         


Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly 
        515                 520                 525             


Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu 
    530                 535                 540                 


His Met Gln Ala Leu Pro Pro Arg 
545                 550         


<210>  44
<211>  574
<212>  PRT
<213>  Artificial

<220>
<223>  4D5-IgG4 -CD8TM-41BB with signal sequence

<400>  44

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
        35                  40                  45              


Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
        115                 120                 125             


Lys Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 
    130                 135                 140                 


Thr Lys Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 
145                 150                 155                 160 


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Ser Leu 
                165                 170                 175     


Pro Asp Tyr Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
            180                 185                 190         


Glu Trp Val Ala Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp 
        195                 200                 205             


Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr 
    210                 215                 220                 


Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ser Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
                245                 250                 255     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Ser Lys Tyr Gly 
            260                 265                 270         


Pro Pro Cys Pro Pro Cys Pro Gly Gly Gly Ser Ser Gly Gly Gly Ser 
        275                 280                 285             


Gly Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln 
    290                 295                 300                 


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
305                 310                 315                 320 


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
                325                 330                 335     


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
            340                 345                 350         


Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu 
        355                 360                 365             


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
    370                 375                 380                 


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Ile Tyr Ile Trp 
385                 390                 395                 400 


Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile 
                405                 410                 415     


Thr Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe 
            420                 425                 430         


Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg 
        435                 440                 445             


Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Gly Gly Gly Arg Val 
    450                 455                 460                 


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn 
465                 470                 475                 480 


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
                485                 490                 495     


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
            500                 505                 510         


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
        515                 520                 525             


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
    530                 535                 540                 


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
545                 550                 555                 560 


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
                565                 570                 


<210>  45
<211>  530
<212>  PRT
<213>  Artificial

<220>
<223>  VH4Vk1-IgG4 -CD8TM-41BB

<400>  45

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Gln Val Gln 
        115                 120                 125             


Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Thr Leu Ser 
    130                 135                 140                 


Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Ile Gly Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Val 
            180                 185                 190         


Thr Ile Ser Val Asp Asn Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser 
        195                 200                 205             


Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
                245                 250                 255     


Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
            260                 265                 270         


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
        275                 280                 285             


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
    290                 295                 300                 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
305                 310                 315                 320 


Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                325                 330                 335     


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
            340                 345                 350         


Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 
        355                 360                 365             


Ser Leu Val Ile Thr Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe 
    370                 375                 380                 


Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly 
385                 390                 395                 400 


Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Gly 
                405                 410                 415     


Gly Gly Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln 
            420                 425                 430         


Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu 
        435                 440                 445             


Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly 
    450                 455                 460                 


Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu 
465                 470                 475                 480 


Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly 
                485                 490                 495     


Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser 
            500                 505                 510         


Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro 
        515                 520                 525             


Pro Arg 
    530 


<210>  46
<211>  552
<212>  PRT
<213>  Artificial

<220>
<223>  VH4Vk1-IgG4 - CD8TM-41BB

<400>  46

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
        35                  40                  45              


Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Gln Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
        115                 120                 125             


Lys Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 
    130                 135                 140                 


Thr Lys Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Ala 
145                 150                 155                 160 


Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu 
                165                 170                 175     


Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu 
            180                 185                 190         


Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser 
        195                 200                 205             


Ala Leu Lys Ser Arg Val Thr Ile Ser Val Asp Asn Ser Lys Asn Gln 
    210                 215                 220                 


Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
                245                 250                 255     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu 
            260                 265                 270         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
        275                 280                 285             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    290                 295                 300                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
305                 310                 315                 320 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
                325                 330                 335     


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
            340                 345                 350         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        355                 360                 365             


Ser Leu Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr 
    370                 375                 380                 


Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Lys Arg Gly Arg Lys 
385                 390                 395                 400 


Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr 
                405                 410                 415     


Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu 
            420                 425                 430         


Gly Gly Cys Glu Leu Gly Gly Gly Arg Val Lys Phe Ser Arg Ser Ala 
        435                 440                 445             


Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu 
    450                 455                 460                 


Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly 
465                 470                 475                 480 


Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu 
                485                 490                 495     


Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser 
            500                 505                 510         


Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly 
        515                 520                 525             


Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu 
    530                 535                 540                 


His Met Gln Ala Leu Pro Pro Arg 
545                 550         


<210>  47
<211>  530
<212>  PRT
<213>  Artificial

<220>
<223>  4D5-IgG4 - CD8TM-41BB

<400>  47

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Ser Thr Ser Gly 
            100                 105                 110         


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Gln 
        115                 120                 125             


Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
    130                 135                 140                 


Leu Ser Cys Ala Ala Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
145                 150                 155                 160 


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile 
                165                 170                 175     


Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
            180                 185                 190         


Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn 
        195                 200                 205             


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ser Arg His Tyr 
    210                 215                 220                 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
225                 230                 235                 240 


Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
                245                 250                 255     


Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
            260                 265                 270         


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
        275                 280                 285             


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
    290                 295                 300                 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
305                 310                 315                 320 


Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                325                 330                 335     


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
            340                 345                 350         


Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 
        355                 360                 365             


Ser Leu Val Ile Thr Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe 
    370                 375                 380                 


Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly 
385                 390                 395                 400 


Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Gly 
                405                 410                 415     


Gly Gly Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln 
            420                 425                 430         


Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu 
        435                 440                 445             


Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly 
    450                 455                 460                 


Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu 
465                 470                 475                 480 


Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly 
                485                 490                 495     


Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser 
            500                 505                 510         


Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro 
        515                 520                 525             


Pro Arg 
    530 


<210>  48
<211>  552
<212>  PRT
<213>  Artificial

<220>
<223>  4D5-IgG4 -CD8TM-41BB with signal sequence

<400>  48

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
        35                  40                  45              


Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
        115                 120                 125             


Lys Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 
    130                 135                 140                 


Thr Lys Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 
145                 150                 155                 160 


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Ser Leu 
                165                 170                 175     


Pro Asp Tyr Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
            180                 185                 190         


Glu Trp Val Ala Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp 
        195                 200                 205             


Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr 
    210                 215                 220                 


Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ser Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
                245                 250                 255     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu 
            260                 265                 270         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
        275                 280                 285             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    290                 295                 300                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
305                 310                 315                 320 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
                325                 330                 335     


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
            340                 345                 350         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        355                 360                 365             


Ser Leu Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr 
    370                 375                 380                 


Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Lys Arg Gly Arg Lys 
385                 390                 395                 400 


Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr 
                405                 410                 415     


Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu 
            420                 425                 430         


Gly Gly Cys Glu Leu Gly Gly Gly Arg Val Lys Phe Ser Arg Ser Ala 
        435                 440                 445             


Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu 
    450                 455                 460                 


Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly 
465                 470                 475                 480 


Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu 
                485                 490                 495     


Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser 
            500                 505                 510         


Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly 
        515                 520                 525             


Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu 
    530                 535                 540                 


His Met Gln Ala Leu Pro Pro Arg 
545                 550         


<210>  49
<211>  120
<212>  PRT
<213>  Homo sapiens

<400>  49

Trp Arg Arg Lys Arg Lys Glu Lys Gln Ser Glu Thr Ser Pro Lys Glu 
1               5                   10                  15      


Phe Leu Thr Ile Tyr Glu Asp Val Lys Asp Leu Lys Thr Arg Arg Asn 
            20                  25                  30          


His Glu Gln Glu Gln Thr Phe Pro Gly Gly Gly Ser Thr Ile Tyr Ser 
        35                  40                  45              


Met Ile Gln Ser Gln Ser Ser Ala Pro Thr Ser Gln Glu Pro Ala Tyr 
    50                  55                  60                  


Thr Leu Tyr Ser Leu Ile Gln Pro Ser Arg Lys Ser Gly Ser Arg Lys 
65                  70                  75                  80  


Arg Asn His Ser Pro Ser Phe Asn Ser Thr Ile Tyr Glu Val Ile Gly 
                85                  90                  95      


Lys Ser Gln Pro Lys Ala Gln Asn Pro Ala Arg Leu Ser Arg Lys Glu 
            100                 105                 110         


Leu Glu Asn Phe Asp Val Tyr Ser 
        115                 120 


<210>  50
<211>  110
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv light chain variable region

<400>  50

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gly Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Ser Thr 
            100                 105                 110 


<210>  51
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv CDR1

<400>  51

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn 
1               5                   10      


<210>  52
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv CDR2

<400>  52

His Thr Ser Arg Leu His Ser 
1               5           


<210>  53
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv CDR3

<400>  53

Gln Gln Gly Asn Thr Leu Pro Tyr Thr 
1               5                   


<210>  54
<211>  120
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv heavy chain variable region

<400>  54

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln 
1               5                   10                  15      


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr 
            20                  25                  30          


Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys 
    50                  55                  60                  


Ser Arg Val Thr Ile Ser Val Asp Asn Ser Lys Asn Gln Phe Ser Leu 
65                  70                  75                  80  


Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  55
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv CDR1

<400>  55

Asp Tyr Gly Val Ser 
1               5   


<210>  56
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv CDR2

<400>  56

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser 
1               5                   10                  15      


<210>  57
<211>  12
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv CDR3

<400>  57

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
1               5                   10          


<210>  58
<211>  110
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv light chain variable region

<400>  58

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Ser Thr 
            100                 105                 110 


<210>  59
<211>  120
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv heavy chain variable region

<400>  59

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Ser Leu Pro Asp Tyr 
            20                  25                  30          


Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ser 
                85                  90                  95      


Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  60
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  CD19 scFv CDR2

<400>  60

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ala Asp Ser Val Lys Gly 
1               5                   10                  15      


<210>  61
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  61

Pro Phe Phe Phe Cys Cys Phe Ile Ala Val Ala Met Gly Ile Arg Phe 
1               5                   10                  15      


Ile Ile Met Val Ala 
            20      


