0 5 Human human JJ 6 9 MHC MHC NNP 10 15 class class NN 16 18 II ii CD 19 23 gene gene NN 24 37 transcription transcription NN 38 46 directed direct VBN 47 49 by by IN 50 53 the the DT 54 62 carboxyl carboxyl NN 63 71 terminus terminus NN 72 74 of of IN 75 80 CIITA CIITA NNP 80 81 , , , 82 85 one one CD 86 88 of of IN 89 92 the the DT 93 102 defective defective JJ 103 108 genes gene NNS 109 111 in in IN 112 116 type type NN 117 119 II ii CD 120 123 MHC MHC NNP 124 132 combined combined JJ 133 139 immune immune JJ 140 150 deficiency deficiency NN 150 151 . . . 153 157 Type type NN 158 160 II ii CD 161 166 major major JJ 167 185 histocompatibility histocompatibility NN 186 193 complex complex NN 194 202 combined combined JJ 203 209 immune immune JJ 210 220 deficiency deficiency NN 221 222 ( ( ( 222 226 type type NN 227 229 II ii CD 230 233 MHC MHC NNP 234 237 CID CID NNP 238 240 or or CC 241 245 bare bare JJ 246 256 lymphocyte lymphocyte NN 257 265 syndrome syndrome NN 265 266 ) ) ) 267 269 is be VBZ 270 271 a a DT 272 282 congenital congenital JJ 283 299 immunodeficiency immunodeficiency NN 300 307 disease disease NN 308 321 characterized characterize VBN 322 324 by by IN 325 331 absent absent JJ 332 335 MHC MHC NNP 336 341 class class NN 342 344 II ii CD 345 355 expression expression NN 355 356 . . . 357 361 Four four CD 362 370 distinct distinct JJ 371 386 complementation complementation NN 387 393 groups group NNS 394 398 have have VBP 399 403 been be VBN 404 414 identified identify VBN 414 415 . . . 416 424 Recently recently RB 424 425 , , , 426 429 the the DT 430 439 defective defective JJ 440 444 gene gene NN 445 447 in in IN 448 453 group group NN 454 456 II ii CD 457 461 type type NN 462 464 II ii CD 465 468 MHC MHC NNP 469 472 CID CID NNP 473 476 has have VBZ 477 481 been be VBN 482 490 isolated isolate VBN 491 494 and and CC 495 501 termed term VBN 502 507 CIITA CIITA NNP 507 508 . . . 509 513 Here here RB 513 514 , , , 515 517 we we PRP 518 529 demonstrate demonstrate VBP 530 534 that that IN 535 540 CIITA CIITA NNP 541 543 is be VBZ 544 546 an an DT 547 550 MHC MHC NNP 551 556 class class NN 557 559 II ii CD 560 573 gene-specific gene-specific JJ 574 587 transcription transcription NN 588 597 activator activator NN 597 598 . . . 599 602 The the DT 603 616 transcription transcription NN 617 627 activation activation NN 628 636 function function NN 637 639 is be VBZ 640 648 provided provide VBN 649 651 by by IN 652 655 the the DT 656 666 N-terminal n-terminal JJ 667 673 acidic acidic JJ 674 680 domain domain NN 681 682 ( ( ( 682 687 amino amino NN 688 693 acids acid NNS 694 700 26-137 26-137 CD 700 701 ) ) ) 701 702 , , , 703 708 which which WDT 709 711 is be VBZ 712 726 experimentally experimentally RB 727 739 exchangeable exchangeable JJ 740 744 with with IN 745 746 a a DT 747 759 heterologous heterologous JJ 760 765 viral viral JJ 766 790 transcription-activating transcription-activating JJ 791 797 domain domain NN 797 798 . . . 799 802 The the DT 803 814 specificity specificity NN 815 817 of of IN 818 823 CIITA CIITA NNP 824 827 for for IN 828 833 three three CD 834 839 major major JJ 840 843 MHC MHC NNP 844 849 class class NN 850 852 II ii CD 853 858 genes gene NNS 858 859 , , , 860 862 DR DR NNP 862 863 , , , 864 866 DQ DQ NNP 867 870 and and CC 871 873 DP DP NNP 873 874 , , , 875 877 is be VBZ 878 886 mediated mediate VBN 887 889 by by IN 890 893 its its PRP$ 894 903 remaining remain VBG 904 914 C-terminal c-terminal JJ 915 923 residues residue NNS 924 925 ( ( ( 925 930 amino amino NN 931 936 acids acid NNS 937 945 317-1130 317-1130 CD 945 946 ) ) ) 946 947 . . . 948 951 The the DT 952 967 transactivation transactivation NN 968 970 of of IN 971 979 multiple multiple JJ 980 983 cis cis NN 984 992 elements element NNS 992 993 , , , 994 1004 especially especially RB 1005 1006 S S NNP 1007 1010 and and CC 1011 1013 X2 X2 NNP 1013 1014 , , , 1015 1017 of of IN 1018 1021 the the DT 1022 1024 DR DR NNP 1025 1030 alpha alpha NN 1031 1039 proximal proximal JJ 1040 1048 promoter promoter NN 1049 1051 in in IN 1052 1057 group group NN 1058 1060 II ii CD 1061 1064 CID CID NNP 1065 1070 cells cell NNS 1071 1073 is be VBZ 1074 1079 CIITA CIITA NNP 1080 1089 dependent dependent JJ 1089 1090 . . . 1091 1096 Since since IN 1097 1102 CIITA CIITA NNP 1103 1117 overexpression overexpression NN 1118 1120 in in IN 1121 1127 normal normal JJ 1128 1133 cells cell NNS 1134 1137 did do VBD 1138 1141 not not RB 1142 1150 increase increase VB 1151 1156 class class NN 1157 1159 II ii CD 1160 1170 expression expression NN 1170 1171 , , , 1172 1174 we we PRP 1175 1182 propose propose VBP 1183 1187 that that IN 1188 1198 initiation initiation NN 1199 1201 of of IN 1202 1207 CIITA CIITA NNP 1208 1218 expression expression NN 1219 1225 serves serve VBZ 1226 1228 as as IN 1229 1232 the the DT 1233 1239 on-off on-off JJ 1240 1246 switch switch NN 1246 1247 , , , 1248 1253 while while IN 1254 1266 availability availability NN 1267 1269 of of IN 1270 1280 downstream downstream JJ 1281 1294 interactor(s) interactor(s) NN 1295 1301 limits limit VBZ 1302 1315 transcription transcription NN 1315 1316 . . .