SEQUENCE LISTING

<110> Cellectis

<120>  METHOD FOR IMPROVING PRODUCTION OF CAR T CELLS

<130>  P81705098PCT00

<150>  US62611987
<151>  2017-12-29

<150>  PA201870015
<151>  2018-01-10

<160> 22

<170> PatentIn version 3.5

<210>  1

<211>  63
<212>  DNA
<213>  artificial sequence

<220>
<223>  CD8 signal seq

<400>  1
atggctttgc ctgtcactgc cttgctgctt ccacttgctc tgttgttgca cgccgcaaga     60
ccc                                                                   63


<210>  2

<211>  723
<212>  DNA
<213>  artificial sequence

<220>
<223>  anti-CD3 scFv

<400>  2
gatattcaga tgacccagtc cccctcctcc ctgtccgctt ccgtcggcga tagagtcacc     60
attacctgtt cagccagtag ttccgtgtct tacatgaact ggtatcagca gaccccaggc    120
aaggcaccta agcggtggat ctacgacaca tccaagctgg cctctggagt gcccagccgg    180
ttctccggct ctggcagcgg caccgactat acctttacaa tcagctccct gcagcctgag    240
gacatcgcca catactattg ccagcagtgg tctagcaatc cattcacctt tggccaggga    300
acaaagctgc agatcggagg aggaggcagc ggcggaggag gctccggcgg cggcggctct    360
caggtgcagc tggtgcagtc cggaggagga gtggtgcagc ccggcagaag cctgcggctg    420
agctgtaagg ccagcggcta caccttcaca cggtatacca tgcactgggt gagacaggca    480
ccaggcaagg gcctggagtg gatcggctac atcaacccca gcagaggcta cacaaactat    540
aatcagaagg tgaaggacag gttcaccatc tcccgcgata actctaagaa tacagccttt    600
ctgcagatgg actccctgag gcctgaggat accggcgtgt atttttgcgc ccgctattat    660
gatgaccatt actgtctgga ctattggggg cagggaacac ccgtgactgt gagctcggat    720
ccc                                                                  723


<210>  3

<211>  135
<212>  DNA
<213>  artificial sequence

<220>
<223>  CD8 hinge

<400>  3
accacaaccc ccgctccaag gccccctacc cccgcaccaa ctattgcctc ccagccactc     60
tcactgcggc ctgaggcctg tcggcccgct gctggaggcg cagtgcatac aaggggcctc    120
gatttcgcct gcgat                                                     135


<210>  4

<211>  72
<212>  DNA
<213>  artificial sequence

<220>
<223>  CD8 trans

<400>  4
atttacatct gggcacccct cgccggcacc tgcggggtgc ttctcctctc cctggtgatt     60
accctgtatt gc                                                         72


<210>  5

<211>  465
<212>  DNA
<213>  artificial sequence

<220>
<223>  41BB-CD3z

<400>  5
agacggggcc ggaagaagct cctctacatt tttaagcagc ctttcatgcg gccagtgcag     60
acaacccaag aggaggatgg gtgttcctgc agattccctg aggaagagga aggcgggtgc    120
gagctgagag tgaagttctc caggagcgca gatgcccccg cctatcaaca gggccagaac    180
cagctctaca acgagcttaa cctcgggagg cgcgaagaat acgacgtgtt ggataagaga    240
agggggcggg accccgagat gggaggaaag ccccggagga agaaccctca ggagggcctg    300
tacaacgagc tgcagaagga taagatggcc gaggcctact cagagatcgg gatgaagggg    360
gagcggcgcc gcgggaaggg gcacgatggg ctctaccagg ggctgagcac agccacaaag    420
gacacatacg acgccttgca catgcaggcc cttccacccc gggaa                    465


<210>  6

<211>  75
<212>  DNA
<213>  artificial sequence

<220>
<223>  2A

<400>  6
tcccatggag gaagcggaga gggacgagga agcctgctga cctgcgggga cgtggaggaa     60
aacccaggac ctcat                                                      75


<210>  7

<211>  702
<212>  DNA
<213>  artificial sequence

<220>
<223>  BFP

<400>  7
atgatgagcg agctgattaa ggagaacatg cacatgaagc tgtacatgga gggcaccgtg     60
gacaaccatc acttcaagtg cacatccgag ggcgaaggca agccctacga gggcacccag    120
accatgagaa tcaaggtggt cgagggcggc cctctcccct tcgccttcga catcctggct    180
actagcttcc tctacggcag caagaccttc atcaaccaca cccagggcat ccccgacttc    240
ttcaagcagt ccttccctga gggcttcaca tgggagagag tcaccacata cgaggacggg    300
ggcgtgctga ccgctaccca ggacaccagc ctccaggacg gctgcctcat ctacaacgtc    360
aagatcagag gggtgaactt cacatccaac ggccctgtga tgcagaagaa aacactcggc    420
tgggaggcct tcaccgagac gctgtacccc gctgacggcg gcctggaagg cagaaacgac    480
atggccctga agctcgtggg cgggagccat ctgatcgcaa acatcaagac cacatataga    540
tccaagaaac ccgctaagaa cctcaagatg cctggcgtct actatgtgga ctacagactg    600
gaaagaatca aggaggccaa caacgagacc tacgtcgagc agcacgaggt ggcagtggcc    660
agatactgcg acctccctag caaactgggg cacaagctga at                       702


<210>  8

<211>  2235
<212>  DNA
<213>  artificial sequence

<220>
<223>  30527

<400>  8
atggctttgc ctgtcactgc cttgctgctt ccacttgctc tgttgttgca cgccgcaaga     60
cccgatattc agatgaccca gtccccctcc tccctgtccg cttccgtcgg cgatagagtc    120
accattacct gttcagccag tagttccgtg tcttacatga actggtatca gcagacccca    180
ggcaaggcac ctaagcggtg gatctacgac acatccaagc tggcctctgg agtgcccagc    240
cggttctccg gctctggcag cggcaccgac tataccttta caatcagctc cctgcagcct    300
gaggacatcg ccacatacta ttgccagcag tggtctagca atccattcac ctttggccag    360
ggaacaaagc tgcagatcgg aggaggaggc agcggcggag gaggctccgg cggcggcggc    420
tctcaggtgc agctggtgca gtccggagga ggagtggtgc agcccggcag aagcctgcgg    480
ctgagctgta aggccagcgg ctacaccttc acacggtata ccatgcactg ggtgagacag    540
gcaccaggca agggcctgga gtggatcggc tacatcaacc ccagcagagg ctacacaaac    600
tataatcaga aggtgaagga caggttcacc atctcccgcg ataactctaa gaatacagcc    660
tttctgcaga tggactccct gaggcctgag gataccggcg tgtatttttg cgcccgctat    720
tatgatgacc attactgtct ggactattgg gggcagggaa cacccgtgac tgtgagctcg    780
gatcccacca caacccccgc tccaaggccc cctacccccg caccaactat tgcctcccag    840
ccactctcac tgcggcctga ggcctgtcgg cccgctgctg gaggcgcagt gcatacaagg    900
ggcctcgatt tcgcctgcga tatttacatc tgggcacccc tcgccggcac ctgcggggtg    960
cttctcctct ccctggtgat taccctgtat tgcagacggg gccggaagaa gctcctctac   1020
atttttaagc agcctttcat gcggccagtg cagacaaccc aagaggagga tgggtgttcc   1080
tgcagattcc ctgaggaaga ggaaggcggg tgcgagctga gagtgaagtt ctccaggagc   1140
gcagatgccc ccgcctatca acagggccag aaccagctct acaacgagct taacctcggg   1200
aggcgcgaag aatacgacgt gttggataag agaagggggc gggaccccga gatgggagga   1260
aagccccgga ggaagaaccc tcaggagggc ctgtacaacg agctgcagaa ggataagatg   1320
gccgaggcct actcagagat cgggatgaag ggggagcggc gccgcgggaa ggggcacgat   1380
gggctctacc aggggctgag cacagccaca aaggacacat acgacgcctt gcacatgcag   1440
gcccttccac cccgggaatc ccatggagga agcggagagg gacgaggaag cctgctgacc   1500
tgcggggacg tggaggaaaa cccaggacct catatgatga gcgagctgat taaggagaac   1560
atgcacatga agctgtacat ggagggcacc gtggacaacc atcacttcaa gtgcacatcc   1620
gagggcgaag gcaagcccta cgagggcacc cagaccatga gaatcaaggt ggtcgagggc   1680
ggccctctcc ccttcgcctt cgacatcctg gctactagct tcctctacgg cagcaagacc   1740
ttcatcaacc acacccaggg catccccgac ttcttcaagc agtccttccc tgagggcttc   1800
acatgggaga gagtcaccac atacgaggac gggggcgtgc tgaccgctac ccaggacacc   1860
agcctccagg acggctgcct catctacaac gtcaagatca gaggggtgaa cttcacatcc   1920
aacggccctg tgatgcagaa gaaaacactc ggctgggagg ccttcaccga gacgctgtac   1980
cccgctgacg gcggcctgga aggcagaaac gacatggccc tgaagctcgt gggcgggagc   2040
catctgatcg caaacatcaa gaccacatat agatccaaga aacccgctaa gaacctcaag   2100
atgcctggcg tctactatgt ggactacaga ctggaaagaa tcaaggaggc caacaacgag   2160
acctacgtcg agcagcacga ggtggcagtg gccagatact gcgacctccc tagcaaactg   2220
gggcacaagc tgaat                                                    2235


<210>  9

<211>  17
<212>  DNA
<213>  artificial sequence

<220>
<223>  T7 promoter

<400>  9
taatacgact cactata                                                    17


<210>  10

<211>  93
<212>  DNA
<213>  artificial sequence

<220>
<223>  mouse hba 3UTR

<400>  10
gctgccttct gcggggcttg ccttctggcc atgcccttct tctctccctt gcacctgtac     60
ctcttggtct ttgaataaag cctgagtagg aag                                  93


<210>  11

<211>  125
<212>  DNA
<213>  artificial sequence

<220>
<223>  120A polyA

<400>  11
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa     60
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa    120
aaaaa                                                                125


<210>  12

<211>  2527
<212>  DNA
<213>  artificial sequence

<220>
<223>  30697

<400>  12
taatacgact cactataggc tagcgccgcc accatggctt tgcctgtcac tgccttgctg     60
cttccacttg ctctgttgtt gcacgccgca agacccgata ttcagatgac ccagtccccc    120
tcctccctgt ccgcttccgt cggcgataga gtcaccatta cctgttcagc cagtagttcc    180
gtgtcttaca tgaactggta tcagcagacc ccaggcaagg cacctaagcg gtggatctac    240
gacacatcca agctggcctc tggagtgccc agccggttct ccggctctgg cagcggcacc    300
gactatacct ttacaatcag ctccctgcag cctgaggaca tcgccacata ctattgccag    360
cagtggtcta gcaatccatt cacctttggc cagggaacaa agctgcagat cggaggagga    420
ggcagcggcg gaggaggctc cggcggcggc ggctctcagg tgcagctggt gcagtccgga    480
ggaggagtgg tgcagcccgg cagaagcctg cggctgagct gtaaggccag cggctacacc    540
ttcacacggt ataccatgca ctgggtgaga caggcaccag gcaagggcct ggagtggatc    600
ggctacatca accccagcag aggctacaca aactataatc agaaggtgaa ggacaggttc    660
accatctccc gcgataactc taagaataca gcctttctgc agatggactc cctgaggcct    720
gaggataccg gcgtgtattt ttgcgcccgc tattatgatg accattactg tctggactat    780
tgggggcagg gaacacccgt gactgtgagc tcggatccca ccacaacccc cgctccaagg    840
ccccctaccc ccgcaccaac tattgcctcc cagccactct cactgcggcc tgaggcctgt    900
cggcccgctg ctggaggcgc agtgcataca aggggcctcg atttcgcctg cgatatttac    960
atctgggcac ccctcgccgg cacctgcggg gtgcttctcc tctccctggt gattaccctg   1020
tattgcagac ggggccggaa gaagctcctc tacattttta agcagccttt catgcggcca   1080
gtgcagacaa cccaagagga ggatgggtgt tcctgcagat tccctgagga agaggaaggc   1140
gggtgcgagc tgagagtgaa gttctccagg agcgcagatg cccccgccta tcaacagggc   1200
cagaaccagc tctacaacga gcttaacctc gggaggcgcg aagaatacga cgtgttggat   1260
aagagaaggg ggcgggaccc cgagatggga ggaaagcccc ggaggaagaa ccctcaggag   1320
ggcctgtaca acgagctgca gaaggataag atggccgagg cctactcaga gatcgggatg   1380
aagggggagc ggcgccgcgg gaaggggcac gatgggctct accaggggct gagcacagcc   1440
acaaaggaca catacgacgc cttgcacatg caggcccttc caccccggga atcccatgga   1500
ggaagcggag agggacgagg aagcctgctg acctgcgggg acgtggagga aaacccagga   1560
cctcatatga tgagcgagct gattaaggag aacatgcaca tgaagctgta catggagggc   1620
accgtggaca accatcactt caagtgcaca tccgagggcg aaggcaagcc ctacgagggc   1680
acccagacca tgagaatcaa ggtggtcgag ggcggccctc tccccttcgc cttcgacatc   1740
ctggctacta gcttcctcta cggcagcaag accttcatca accacaccca gggcatcccc   1800
gacttcttca agcagtcctt ccctgagggc ttcacatggg agagagtcac cacatacgag   1860
gacgggggcg tgctgaccgc tacccaggac accagcctcc aggacggctg cctcatctac   1920
aacgtcaaga tcagaggggt gaacttcaca tccaacggcc ctgtgatgca gaagaaaaca   1980
ctcggctggg aggccttcac cgagacgctg taccccgctg acggcggcct ggaaggcaga   2040
aacgacatgg ccctgaagct cgtgggcggg agccatctga tcgcaaacat caagaccaca   2100
tatagatcca agaaacccgc taagaacctc aagatgcctg gcgtctacta tgtggactac   2160
agactggaaa gaatcaagga ggccaacaac gagacctacg tcgagcagca cgaggtggca   2220
gtggccagat actgcgacct ccctagcaaa ctggggcaca agctgaattg acggccgact   2280
gataactcga ggctgccttc tgcggggctt gccttctggc catgcccttc ttctctccct   2340
tgcacctgta cctcttggtc tttgaataaa gcctgagtag gaaggtcgag gcggccaaca   2400
acaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   2460
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   2520
aaaaaaa                                                             2527


<210>  13

<211>  56
<212>  DNA
<213>  artificial sequence

<220>
<223>  oligo1

<400>  13
gcatcgtaat acgactcact atagggcagg ccaccatggc tttgcctgtc actgcc         56


<210>  14

<211>  21
<212>  DNA
<213>  artificial sequence

<220>
<223>  oligo2

<400>  14
tcaattcagc ttgtgcccca g                                               21


<210>  15

<211>  21
<212>  PRT
<213>  artificial sequence

<220>
<223>  CD8 signal seq

<400>  15
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      


His Ala Ala Arg Pro 
            20      


<210>  16

<211>  241
<212>  PRT
<213>  artificial sequence

<220>
<223>  anti-CD3 scFv

<400>  16
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 Ser Ala Ser Ser Ser Val Ser Tyr Met 
            20                  25                  30          


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


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


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


Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Phe Thr 
                85                  90                  95      


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


Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly 
        115                 120                 125             


Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Lys Ala 
    130                 135                 140                 


Ser Gly Tyr Thr Phe Thr Arg Tyr Thr Met His Trp Val Arg Gln Ala 
145                 150                 155                 160 


Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly 
                165                 170                 175     


Tyr Thr Asn Tyr Asn Gln Lys Val Lys Asp Arg Phe Thr Ile Ser Arg 
            180                 185                 190         


Asp Asn Ser Lys Asn Thr Ala Phe Leu Gln Met Asp Ser Leu Arg Pro 
        195                 200                 205             


Glu Asp Thr Gly Val Tyr Phe Cys Ala Arg Tyr Tyr Asp Asp His Tyr 
    210                 215                 220                 


Cys Leu Asp Tyr Trp Gly Gln Gly Thr Pro Val Thr Val Ser Ser Asp 
225                 230                 235                 240 


Pro 
    


<210>  17

<211>  45
<212>  PRT
<213>  artificial sequence

<220>
<223>  CD8 hinge

<400>  17
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>  18

<211>  24
<212>  PRT
<213>  artificial sequence

<220>
<223>  CD8 trans

<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 Cys 
            20                  


<210>  19

<211>  155
<212>  PRT
<213>  artificial sequence

<220>
<223>  41BB-CD3z

<400>  19
Arg 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 Arg Val Lys Phe Ser Arg 
        35                  40                  45              


Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn 
    50                  55                  60                  


Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg 
65                  70                  75                  80  


Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro 
                85                  90                  95      


Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala 
            100                 105                 110         


Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His 
        115                 120                 125             


Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp 
    130                 135                 140                 


Ala Leu His Met Gln Ala Leu Pro Pro Arg Glu 
145                 150                 155 


<210>  20

<211>  25
<212>  PRT
<213>  artificial sequence

<220>
<223>  2A

<400>  20
Ser His Gly Gly Ser Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly 
1               5                   10                  15      


Asp Val Glu Glu Asn Pro Gly Pro His 
            20                  25  


<210>  21

<211>  234
<212>  PRT
<213>  artificial sequence

<220>
<223>  BFP

<400>  21
Met Met Ser Glu Leu Ile Lys Glu Asn Met His Met Lys Leu Tyr Met 
1               5                   10                  15      


Glu Gly Thr Val Asp Asn His His Phe Lys Cys Thr Ser Glu Gly Glu 
            20                  25                  30          


Gly Lys Pro Tyr Glu Gly Thr Gln Thr Met Arg Ile Lys Val Val Glu 
        35                  40                  45              


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


Tyr Gly Ser Lys Thr Phe Ile Asn His Thr Gln Gly Ile Pro Asp Phe 
65                  70                  75                  80  


Phe Lys Gln Ser Phe Pro Glu Gly Phe Thr Trp Glu Arg Val Thr Thr 
                85                  90                  95      


Tyr Glu Asp Gly Gly Val Leu Thr Ala Thr Gln Asp Thr Ser Leu Gln 
            100                 105                 110         


Asp Gly Cys Leu Ile Tyr Asn Val Lys Ile Arg Gly Val Asn Phe Thr 
        115                 120                 125             


Ser Asn Gly Pro Val Met Gln Lys Lys Thr Leu Gly Trp Glu Ala Phe 
    130                 135                 140                 


Thr Glu Thr Leu Tyr Pro Ala Asp Gly Gly Leu Glu Gly Arg Asn Asp 
145                 150                 155                 160 


Met Ala Leu Lys Leu Val Gly Gly Ser His Leu Ile Ala Asn Ile Lys 
                165                 170                 175     


Thr Thr Tyr Arg Ser Lys Lys Pro Ala Lys Asn Leu Lys Met Pro Gly 
            180                 185                 190         


Val Tyr Tyr Val Asp Tyr Arg Leu Glu Arg Ile Lys Glu Ala Asn Asn 
        195                 200                 205             


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


Leu Pro Ser Lys Leu Gly His Lys Leu Asn 
225                 230                 


<210>  22

<211>  745
<212>  PRT
<213>  artificial sequence

<220>
<223>  30527

<400>  22
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      


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


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


Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Thr Pro Gly Lys Ala Pro 
    50                  55                  60                  


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


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr Ile Ser 
                85                  90                  95      


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


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


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln 
    130                 135                 140                 


Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 
145                 150                 155                 160 


Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr Thr Met His 
                165                 170                 175     


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile 
            180                 185                 190         


Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Asn Gln Lys Val Lys Asp Arg 
        195                 200                 205             


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


Asp Ser Leu Arg Pro Glu Asp Thr Gly Val Tyr Phe Cys Ala Arg Tyr 
225                 230                 235                 240 


Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly Thr Pro Val 
                245                 250                 255     


Thr Val Ser Ser Asp Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr 
            260                 265                 270         


Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala 
        275                 280                 285             


Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe 
    290                 295                 300                 


Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val 
305                 310                 315                 320 


Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Arg Arg Gly Arg Lys 
                325                 330                 335     


Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr 
            340                 345                 350         


Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu 
        355                 360                 365             


Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro 
    370                 375                 380                 


Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly 
385                 390                 395                 400 


Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro 
                405                 410                 415     


Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr 
            420                 425                 430         


Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly 
        435                 440                 445             


Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln 
    450                 455                 460                 


Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln 
465                 470                 475                 480 


Ala Leu Pro Pro Arg Glu Ser His Gly Gly Ser Gly Glu Gly Arg Gly 
                485                 490                 495     


Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly Pro His Met 
            500                 505                 510         


Met Ser Glu Leu Ile Lys Glu Asn Met His Met Lys Leu Tyr Met Glu 
        515                 520                 525             


Gly Thr Val Asp Asn His His Phe Lys Cys Thr Ser Glu Gly Glu Gly 
    530                 535                 540                 


Lys Pro Tyr Glu Gly Thr Gln Thr Met Arg Ile Lys Val Val Glu Gly 
545                 550                 555                 560 


Gly Pro Leu Pro Phe Ala Phe Asp Ile Leu Ala Thr Ser Phe Leu Tyr 
                565                 570                 575     


Gly Ser Lys Thr Phe Ile Asn His Thr Gln Gly Ile Pro Asp Phe Phe 
            580                 585                 590         


Lys Gln Ser Phe Pro Glu Gly Phe Thr Trp Glu Arg Val Thr Thr Tyr 
        595                 600                 605             


Glu Asp Gly Gly Val Leu Thr Ala Thr Gln Asp Thr Ser Leu Gln Asp 
    610                 615                 620                 


Gly Cys Leu Ile Tyr Asn Val Lys Ile Arg Gly Val Asn Phe Thr Ser 
625                 630                 635                 640 


Asn Gly Pro Val Met Gln Lys Lys Thr Leu Gly Trp Glu Ala Phe Thr 
                645                 650                 655     


Glu Thr Leu Tyr Pro Ala Asp Gly Gly Leu Glu Gly Arg Asn Asp Met 
            660                 665                 670         


Ala Leu Lys Leu Val Gly Gly Ser His Leu Ile Ala Asn Ile Lys Thr 
        675                 680                 685             


Thr Tyr Arg Ser Lys Lys Pro Ala Lys Asn Leu Lys Met Pro Gly Val 
    690                 695                 700                 


Tyr Tyr Val Asp Tyr Arg Leu Glu Arg Ile Lys Glu Ala Asn Asn Glu 
705                 710                 715                 720 


Thr Tyr Val Glu Gln His Glu Val Ala Val Ala Arg Tyr Cys Asp Leu 
                725                 730                 735     


Pro Ser Lys Leu Gly His Lys Leu Asn 
            740                 745 




