                               SEQUENCE LISTING

<110> YU, Jianhua et al.
 
<120> EGFR-DIRECTED CAR THERAPY FOR GLIOBLASTOMA

<130> 113086-0610

<140> PCT/US2016/026057
<141> 2016-04-05

<150> 62/143,744
<151> 2015-04-06

<160> 31    

<170> PatentIn version 3.5

<210> 1
<211> 48
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      oligonucleotide

<400> 1
ctcgagccca aatcttgtga caaaactcac acatgcccac cgtgcccg                    48


<210> 2
<211> 81
<212> DNA
<213> Unknown

<220>
<223> Description of Unknown:
      CD28 transmembrane region sequence

<400> 2
ttttgggtgc tggtggtggt tggtggagtc ctggcttgct atagcttgct agtaacagtg       60

gcctttatta ttttctgggt g                                                 81


<210> 3
<211> 126
<212> DNA
<213> Unknown

<220>
<223> Description of Unknown: 
      4-1BB co-stimulatory signaling region sequence

<400> 3
aaacggggca gaaagaaact cctgtatata ttcaaacaac catttatgag accagtacaa       60

actactcaag aggaagatgg ctgtagctgc cgatttccag aagaagaaga aggaggatgt      120

gaactg                                                                 126


<210> 4
<211> 123
<212> DNA
<213> Unknown

<220>
<223> Description of Unknown: 
      CD28 co-stimulatory signaling region sequence

<400> 4
aggagtaaga ggagcaggct cctgcacagt gactacatga acatgactcc ccgccgcccc       60

gggcccaccc gcaagcatta ccagccctat gccccaccac gcgacttcgc agcctatcgc      120

tcc                                                                    123


<210> 5
<211> 339
<212> DNA
<213> Unknown

<220>
<223> Description of Unknown: 
      CD3 zeta signaling region sequence

<400> 5
agagtgaagt tcagcaggag cgcagacgcc cccgcgtacc agcagggcca gaaccagctc       60

tataacgagc tcaatctagg acgaagagag gagtacgatg ttttggacaa gagacgtggc      120

cgggaccctg agatgggggg aaagccgaga aggaagaacc ctcaggaagg cctgtacaat      180

gaactgcaga aagataagat ggcggaggcc tacagtgaga ttgggatgaa aggcgagcgc      240

cggaggggca aggggcacga tggcctttac cagggtctca gtacagccac caaggacacc      300

tacgacgccc ttcacatgca ggccctgccc cctcgctaa                             339


<210> 6
<211> 1210
<212> PRT
<213> Homo sapiens

<400> 6
Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 
1               5                   10                  15      


Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 
            20                  25                  30          


Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 
        35                  40                  45              


Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 
    50                  55                  60                  


Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 
65                  70                  75                  80  


Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 
                85                  90                  95      


Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 
            100                 105                 110         


Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 
        115                 120                 125             


Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 
    130                 135                 140                 


His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 
145                 150                 155                 160 


Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 
                165                 170                 175     


Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 
            180                 185                 190         


Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 
        195                 200                 205             


Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 
    210                 215                 220                 


Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 
225                 230                 235                 240 


Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 
                245                 250                 255     


Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 
            260                 265                 270         


Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 
        275                 280                 285             


Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 
    290                 295                 300                 


Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 
305                 310                 315                 320 


Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 
                325                 330                 335     


Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 
            340                 345                 350         


Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 
        355                 360                 365             


Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 
    370                 375                 380                 


Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 
385                 390                 395                 400 


Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 
                405                 410                 415     


Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 
            420                 425                 430         


His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 
        435                 440                 445             


Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 
    450                 455                 460                 


Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 
465                 470                 475                 480 


Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 
                485                 490                 495     


Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 
            500                 505                 510         


Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 
        515                 520                 525             


Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 
    530                 535                 540                 


Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 
545                 550                 555                 560 


Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 
                565                 570                 575     


Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 
            580                 585                 590         


Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 
        595                 600                 605             


Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 
    610                 615                 620                 


Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro Thr Asn Gly 
625                 630                 635                 640 


Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala Leu Leu Leu 
                645                 650                 655     


Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met Arg Arg Arg His 
            660                 665                 670         


Ile Val Arg Lys Arg Thr Leu Arg Arg Leu Leu Gln Glu Arg Glu Leu 
        675                 680                 685             


Val Glu Pro Leu Thr Pro Ser Gly Glu Ala Pro Asn Gln Ala Leu Leu 
    690                 695                 700                 


Arg Ile Leu Lys Glu Thr Glu Phe Lys Lys Ile Lys Val Leu Gly Ser 
705                 710                 715                 720 


Gly Ala Phe Gly Thr Val Tyr Lys Gly Leu Trp Ile Pro Glu Gly Glu 
                725                 730                 735     


Lys Val Lys Ile Pro Val Ala Ile Lys Glu Leu Arg Glu Ala Thr Ser 
            740                 745                 750         


Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met Ala Ser 
        755                 760                 765             


Val Asp Asn Pro His Val Cys Arg Leu Leu Gly Ile Cys Leu Thr Ser 
    770                 775                 780                 


Thr Val Gln Leu Ile Thr Gln Leu Met Pro Phe Gly Cys Leu Leu Asp 
785                 790                 795                 800 


Tyr Val Arg Glu His Lys Asp Asn Ile Gly Ser Gln Tyr Leu Leu Asn 
                805                 810                 815     


Trp Cys Val Gln Ile Ala Lys Gly Met Asn Tyr Leu Glu Asp Arg Arg 
            820                 825                 830         


Leu Val His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Lys Thr Pro 
        835                 840                 845             


Gln His Val Lys Ile Thr Asp Phe Gly Leu Ala Lys Leu Leu Gly Ala 
    850                 855                 860                 


Glu Glu Lys Glu Tyr His Ala Glu Gly Gly Lys Val Pro Ile Lys Trp 
865                 870                 875                 880 


Met Ala Leu Glu Ser Ile Leu His Arg Ile Tyr Thr His Gln Ser Asp 
                885                 890                 895     


Val Trp Ser Tyr Gly Val Thr Val Trp Glu Leu Met Thr Phe Gly Ser 
            900                 905                 910         


Lys Pro Tyr Asp Gly Ile Pro Ala Ser Glu Ile Ser Ser Ile Leu Glu 
        915                 920                 925             


Lys Gly Glu Arg Leu Pro Gln Pro Pro Ile Cys Thr Ile Asp Val Tyr 
    930                 935                 940                 


Met Ile Met Val Lys Cys Trp Met Ile Asp Ala Asp Ser Arg Pro Lys 
945                 950                 955                 960 


Phe Arg Glu Leu Ile Ile Glu Phe Ser Lys Met Ala Arg Asp Pro Gln 
                965                 970                 975     


Arg Tyr Leu Val Ile Gln Gly Asp Glu Arg Met His Leu Pro Ser Pro 
            980                 985                 990         


Thr Asp Ser Asn Phe Tyr Arg Ala  Leu Met Asp Glu Glu  Asp Met Asp 
        995                 1000                 1005             


Asp Val  Val Asp Ala Asp Glu  Tyr Leu Ile Pro Gln  Gln Gly Phe 
    1010                 1015                 1020             


Phe Ser  Ser Pro Ser Thr Ser  Arg Thr Pro Leu Leu  Ser Ser Leu 
    1025                 1030                 1035             


Ser Ala  Thr Ser Asn Asn Ser  Thr Val Ala Cys Ile  Asp Arg Asn 
    1040                 1045                 1050             


Gly Leu  Gln Ser Cys Pro Ile  Lys Glu Asp Ser Phe  Leu Gln Arg 
    1055                 1060                 1065             


Tyr Ser  Ser Asp Pro Thr Gly  Ala Leu Thr Glu Asp  Ser Ile Asp 
    1070                 1075                 1080             


Asp Thr  Phe Leu Pro Val Pro  Glu Tyr Ile Asn Gln  Ser Val Pro 
    1085                 1090                 1095             


Lys Arg  Pro Ala Gly Ser Val  Gln Asn Pro Val Tyr  His Asn Gln 
    1100                 1105                 1110             


Pro Leu  Asn Pro Ala Pro Ser  Arg Asp Pro His Tyr  Gln Asp Pro 
    1115                 1120                 1125             


His Ser  Thr Ala Val Gly Asn  Pro Glu Tyr Leu Asn  Thr Val Gln 
    1130                 1135                 1140             


Pro Thr  Cys Val Asn Ser Thr  Phe Asp Ser Pro Ala  His Trp Ala 
    1145                 1150                 1155             


Gln Lys  Gly Ser His Gln Ile  Ser Leu Asp Asn Pro  Asp Tyr Gln 
    1160                 1165                 1170             


Gln Asp  Phe Phe Pro Lys Glu  Ala Lys Pro Asn Gly  Ile Phe Lys 
    1175                 1180                 1185             


Gly Ser  Thr Ala Glu Asn Ala  Glu Tyr Leu Arg Val  Ala Pro Gln 
    1190                 1195                 1200             


Ser Ser  Glu Phe Ile Gly Ala  
    1205                 1210 


<210> 7
<211> 705
<212> PRT
<213> Homo sapiens

<400> 7
Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 
1               5                   10                  15      


Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 
            20                  25                  30          


Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 
        35                  40                  45              


Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 
    50                  55                  60                  


Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 
65                  70                  75                  80  


Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 
                85                  90                  95      


Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 
            100                 105                 110         


Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 
        115                 120                 125             


Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 
    130                 135                 140                 


His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 
145                 150                 155                 160 


Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 
                165                 170                 175     


Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 
            180                 185                 190         


Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 
        195                 200                 205             


Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 
    210                 215                 220                 


Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 
225                 230                 235                 240 


Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 
                245                 250                 255     


Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 
            260                 265                 270         


Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 
        275                 280                 285             


Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 
    290                 295                 300                 


Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 
305                 310                 315                 320 


Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 
                325                 330                 335     


Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 
            340                 345                 350         


Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 
        355                 360                 365             


Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 
    370                 375                 380                 


Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 
385                 390                 395                 400 


Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 
                405                 410                 415     


Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 
            420                 425                 430         


His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 
        435                 440                 445             


Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 
    450                 455                 460                 


Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 
465                 470                 475                 480 


Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 
                485                 490                 495     


Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 
            500                 505                 510         


Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 
        515                 520                 525             


Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 
    530                 535                 540                 


Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 
545                 550                 555                 560 


Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 
                565                 570                 575     


Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 
            580                 585                 590         


Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 
        595                 600                 605             


Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 
    610                 615                 620                 


Thr Tyr Gly Pro Gly Asn Glu Ser Leu Lys Ala Met Leu Phe Cys Leu 
625                 630                 635                 640 


Phe Lys Leu Ser Ser Cys Asn Gln Ser Asn Asp Gly Ser Val Ser His 
                645                 650                 655     


Gln Ser Gly Ser Pro Ala Ala Gln Glu Ser Cys Leu Gly Trp Ile Pro 
            660                 665                 670         


Ser Leu Leu Pro Ser Glu Phe Gln Leu Gly Trp Gly Gly Cys Ser His 
        675                 680                 685             


Leu His Ala Trp Pro Ser Ala Ser Val Ile Ile Thr Ala Ser Ser Cys 
    690                 695                 700                 


His 
705 


<210> 8
<211> 1200
<212> PRT
<213> Homo sapiens

<400> 8
Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 
1               5                   10                  15      


Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 
            20                  25                  30          


Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 
        35                  40                  45              


Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 
    50                  55                  60                  


Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 
65                  70                  75                  80  


Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 
                85                  90                  95      


Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 
            100                 105                 110         


Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 
        115                 120                 125             


Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 
    130                 135                 140                 


His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 
145                 150                 155                 160 


Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 
                165                 170                 175     


Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 
            180                 185                 190         


Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 
        195                 200                 205             


Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 
    210                 215                 220                 


Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 
225                 230                 235                 240 


Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 
                245                 250                 255     


Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 
            260                 265                 270         


Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 
        275                 280                 285             


Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 
    290                 295                 300                 


Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 
305                 310                 315                 320 


Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 
                325                 330                 335     


Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 
            340                 345                 350         


Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 
        355                 360                 365             


Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 
    370                 375                 380                 


Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 
385                 390                 395                 400 


Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 
                405                 410                 415     


Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 
            420                 425                 430         


His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 
        435                 440                 445             


Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 
    450                 455                 460                 


Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 
465                 470                 475                 480 


Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 
                485                 490                 495     


Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 
            500                 505                 510         


Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 
        515                 520                 525             


Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 
    530                 535                 540                 


Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 
545                 550                 555                 560 


Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 
                565                 570                 575     


Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 
            580                 585                 590         


Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 
        595                 600                 605             


Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 
    610                 615                 620                 


Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro Thr Asn Gly 
625                 630                 635                 640 


Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala Leu Leu Leu 
                645                 650                 655     


Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met Arg Arg Arg His 
            660                 665                 670         


Ile Val Arg Lys Arg Thr Leu Arg Arg Leu Leu Gln Glu Arg Glu Leu 
        675                 680                 685             


Val Glu Pro Leu Thr Pro Ser Gly Glu Ala Pro Asn Gln Ala Leu Leu 
    690                 695                 700                 


Arg Ile Leu Lys Glu Thr Glu Phe Lys Lys Ile Lys Val Leu Gly Ser 
705                 710                 715                 720 


Gly Ala Phe Gly Thr Val Tyr Lys Gly Leu Trp Ile Pro Glu Gly Glu 
                725                 730                 735     


Lys Val Lys Ile Pro Val Ala Ile Lys Glu Leu Arg Glu Ala Thr Ser 
            740                 745                 750         


Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met Ala Ser 
        755                 760                 765             


Val Asp Asn Pro His Val Cys Arg Leu Leu Gly Ile Cys Leu Thr Ser 
    770                 775                 780                 


Thr Val Gln Leu Ile Thr Gln Leu Met Pro Phe Gly Cys Leu Leu Asp 
785                 790                 795                 800 


Tyr Val Arg Glu His Lys Asp Asn Ile Gly Ser Gln Tyr Leu Leu Asn 
                805                 810                 815     


Trp Cys Val Gln Ile Ala Lys Gly Met Asn Tyr Leu Glu Asp Arg Arg 
            820                 825                 830         


Leu Val His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Lys Thr Pro 
        835                 840                 845             


Gln His Val Lys Ile Thr Asp Phe Gly Leu Ala Lys Leu Leu Gly Ala 
    850                 855                 860                 


Glu Glu Lys Glu Tyr His Ala Glu Gly Gly Lys Val Pro Ile Lys Trp 
865                 870                 875                 880 


Met Ala Leu Glu Ser Ile Leu His Arg Ile Tyr Thr His Gln Ser Asp 
                885                 890                 895     


Val Trp Ser Tyr Gly Val Thr Val Trp Glu Leu Met Thr Phe Gly Ser 
            900                 905                 910         


Lys Pro Tyr Asp Gly Ile Pro Ala Ser Glu Ile Ser Ser Ile Leu Glu 
        915                 920                 925             


Lys Gly Glu Arg Leu Pro Gln Pro Pro Ile Cys Thr Ile Asp Val Tyr 
    930                 935                 940                 


Met Ile Met Val Lys Cys Trp Met Ile Asp Ala Asp Ser Arg Pro Lys 
945                 950                 955                 960 


Phe Arg Glu Leu Ile Ile Glu Phe Ser Lys Met Ala Arg Asp Pro Gln 
                965                 970                 975     


Arg Tyr Leu Val Ile Gln Gly Asp Glu Arg Met His Leu Pro Leu Met 
            980                 985                 990         


Asp Glu Glu Asp Met Asp Asp Val  Val Asp Ala Asp Glu  Tyr Leu Ile 
        995                 1000                 1005             


Pro Gln  Gln Gly Phe Phe Ser  Ser Pro Ser Thr Ser  Arg Thr Pro 
    1010                 1015                 1020             


Leu Leu  Ser Ser Leu Ser Ala  Thr Ser Asn Asn Ser  Thr Val Ala 
    1025                 1030                 1035             


Cys Ile  Asp Arg Asn Gly Leu  Gln Ser Cys Pro Ile  Lys Glu Asp 
    1040                 1045                 1050             


Ser Phe  Leu Gln Arg Tyr Ser  Ser Asp Pro Thr Gly  Ala Leu Thr 
    1055                 1060                 1065             


Glu Asp  Ser Ile Asp Asp Thr  Phe Leu Pro Val Pro  Glu Tyr Ile 
    1070                 1075                 1080             


Asn Gln  Ser Val Pro Lys Arg  Pro Ala Gly Ser Val  Gln Asn Pro 
    1085                 1090                 1095             


Val Tyr  His Asn Gln Pro Leu  Asn Pro Ala Pro Ser  Arg Asp Pro 
    1100                 1105                 1110             


His Tyr  Gln Asp Pro His Ser  Thr Ala Val Gly Asn  Pro Glu Tyr 
    1115                 1120                 1125             


Leu Asn  Thr Val Gln Pro Thr  Cys Val Asn Ser Thr  Phe Asp Ser 
    1130                 1135                 1140             


Pro Ala  His Trp Ala Gln Lys  Gly Ser His Gln Ile  Ser Leu Asp 
    1145                 1150                 1155             


Asn Pro  Asp Tyr Gln Gln Asp  Phe Phe Pro Lys Glu  Ala Lys Pro 
    1160                 1165                 1170             


Asn Gly  Ile Phe Lys Gly Ser  Thr Ala Glu Asn Ala  Glu Tyr Leu 
    1175                 1180                 1185             


Arg Val  Ala Pro Gln Ser Ser  Glu Phe Ile Gly Ala  
    1190                 1195                 1200 


<210> 9
<211> 7
<212> PRT
<213> Homo sapiens

<400> 9
Glu Leu Arg Glu Ala Thr Ser 
1               5           


<210> 10
<211> 6
<212> PRT
<213> Homo sapiens

<400> 10
Glu Leu Arg Glu Ala Thr 
1               5       


<210> 11
<211> 51
<212> PRT
<213> Homo sapiens

<400> 11
Pro Ala Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala 
1               5                   10                  15      


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


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


Asp Ile Tyr 
    50      


<210> 12
<211> 49
<212> PRT
<213> Mus musculus

<400> 12
Lys Val Asn Ser Thr Thr Thr Lys Pro Val Leu Arg Thr Pro Ser Pro 
1               5                   10                  15      


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


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


Tyr 
    


<210> 13
<211> 51
<212> PRT
<213> Felis sp.

<400> 13
Pro Val Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Gln Ala 
1               5                   10                  15      


Pro Ile Thr Thr Ser Gln Arg Val Ser Leu Arg Pro Gly Thr Cys Gln 
            20                  25                  30          


Pro Ser Ala Gly Ser Thr Val Glu Ala Ser Gly Leu Asp Leu Ser Cys 
        35                  40                  45              


Asp Ile Tyr 
    50      


<210> 14
<211> 21
<212> PRT
<213> Homo sapiens

<400> 14
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> 15
<211> 21
<212> PRT
<213> Mus musculus

<400> 15
Ile Trp Ala Pro Leu Ala Gly Ile Cys Val Ala Leu Leu Leu Ser Leu 
1               5                   10                  15      


Ile Ile Thr Leu Ile 
            20      


<210> 16
<211> 21
<212> PRT
<213> Rattus norvegicus

<400> 16
Ile Trp Ala Pro Leu Ala Gly Ile Cys Ala Val Leu Leu Leu Ser Leu 
1               5                   10                  15      


Val Ile Thr Leu Ile 
            20      


<210> 17
<211> 42
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 17
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> 18
<211> 220
<212> PRT
<213> Unknown

<220>
<223> Description of Unknown: 
      CD28 polypeptide sequence

<400> 18
Met Leu Arg Leu Leu Leu Ala Leu Asn Leu Phe Pro Ser Ile Gln Val 
1               5                   10                  15      


Thr Gly Asn Lys Ile Leu Val Lys Gln Ser Pro Met Leu Val Ala Tyr 
            20                  25                  30          


Asp Asn Ala Val Asn Leu Ser Cys Lys Tyr Ser Tyr Asn Leu Phe Ser 
        35                  40                  45              


Arg Glu Phe Arg Ala Ser Leu His Lys Gly Leu Asp Ser Ala Val Glu 
    50                  55                  60                  


Val Cys Val Val Tyr Gly Asn Tyr Ser Gln Gln Leu Gln Val Tyr Ser 
65                  70                  75                  80  


Lys Thr Gly Phe Asn Cys Asp Gly Lys Leu Gly Asn Glu Ser Val Thr 
                85                  90                  95      


Phe Tyr Leu Gln Asn Leu Tyr Val Asn Gln Thr Asp Ile Tyr Phe Cys 
            100                 105                 110         


Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser 
        115                 120                 125             


Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro 
    130                 135                 140                 


Leu Phe Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly 
145                 150                 155                 160 


Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile 
                165                 170                 175     


Phe Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met 
            180                 185                 190         


Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro 
        195                 200                 205             


Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
    210                 215                 220 


<210> 19
<211> 105
<212> DNA
<213> Unknown

<220>
<223> Description of Unknown: 
      ICOS costimulatory signaling region sequence

<400> 19
acaaaaaaga agtattcatc cagtgtgcac gaccctaacg gtgaatacat gttcatgaga       60

gcagtgaaca cagccaaaaa atccagactc acagatgtga cccta                      105


<210> 20
<211> 108
<212> DNA
<213> Unknown

<220>
<223> Description of Unknown: 
      OX40 costimulatory signaling region sequence

<400> 20
agggaccaga ggctgccccc cgatgcccac aagccccctg ggggaggcag tttccggacc       60

cccatccaag aggagcaggc cgacgcccac tccaccctgg ccaagatc                   108


<210> 21
<211> 112
<212> PRT
<213> Unknown

<220>
<223> Description of Unknown: 
      CD3 zeta signaling domain sequence

<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> 14
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 22
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
1               5                   10                  


<210> 23
<211> 13
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 23
Glu Phe Gly Ala Gly Leu Val Leu Gly Gly Gln Phe Met 
1               5                   10              


<210> 24
<211> 118
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 24
Gln Val Gln Leu Gln Gln Ser Gly Ser Glu Met Ala Arg Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Leu Pro Cys Lys Ala Ser Gly Asp Thr Phe Thr Ser Tyr 
            20                  25                  30          


Trp Met His Trp Val Lys Gln Arg His Gly His Gly Pro Glu Trp Ile 
        35                  40                  45              


Gly Asn Ile Tyr Pro Gly Ser Gly Gly Thr Asn Tyr Ala Glu Lys Phe 
    50                  55                  60                  


Lys Asn Lys Val Thr Leu Thr Val Asp Arg Ser Ser Arg Thr Val Tyr 
65                  70                  75                  80  


Met His Leu Ser Arg Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                85                  90                  95      


Thr Arg Ser Gly Gly Pro Tyr Phe Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Thr Leu Thr Val Ser Ser 
        115             


<210> 25
<211> 345
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 25
gacattctaa tgacccaatc tccactctcc ctgcctgtca gtcttggaga tcaagcctcc       60

tacctgcaaa ggccaggcca gtctccaaag ctcctgatct acaaagtttc cgaccgattt      120

tacctgcaaa ggccaggcca gtctccaaag ctcctgatct acaaagtttc cgaccgattt      180

tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc      240

agcagagtag aggctgagga tctgggaatt tattactgct ttcaaggttc acatattcct      300

cccacgttcg gaggggggac caagctggaa atcaaacgtg cggcc                      345


<210> 26
<211> 115
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 26
Asp Ile Leu Met Thr Gln Ser Pro Leu Ser Leu Pro Val Ser Leu Gly 
1               5                   10                  15      


Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Asn Ile Val His Asn 
            20                  25                  30          


Asn Gly Ile Thr Tyr Leu Glu Trp Tyr Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Lys Leu Leu Ile Tyr Lys Val Ser Asp Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Leu Gly Ile Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Ser His Ile Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Ala Ala 
        115 


<210> 27
<211> 354
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 27
caggtccagc tgcagcagtc tgggtctgag atggcgaggc ctggagcttc agtgaagctg       60

ccctgcaagg cttctggcga cacattcacc agttactgga tgcactgggt gaagcagagg      120

catggacatg gccctgagtg gatcggaaat atttatccag gtagtggtgg tactaactac      180

gctgagaagt tcaagaacaa ggtcactctg actgtagaca ggtcctcccg cacagtctac      240

atgcacctca gcaggctgac atctgaggac tctgcggtct attattgtac aagatcgggg      300

ggtccctact tctttgacta ctggggccaa ggcaccactc tcacagtctc ctcc            354


<210> 28
<211> 22
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      primer

<400> 28
tgactccgtc cagtattgat cg                                                22


<210> 29
<211> 22
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      primer

<400> 29
gcccttcgca cttcttacac tt                                                22


<210> 30
<211> 21
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      primer

<400> 30
aggtcactct gactgtagac a                                                 21


<210> 31
<211> 21
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      primer

<400> 31
gttcatgtag tcactgtgca g                                                 21


