0 2 An an DT 3 19 isotype-specific isotype-specific JJ 20 29 activator activator NN 30 32 of of IN 33 38 major major JJ 39 57 histocompatibility histocompatibility NN 58 65 complex complex NN 66 67 ( ( ( 67 70 MHC MHC NNP 70 71 ) ) ) 72 77 class class NN 78 80 II ii CD 81 86 genes gene NNS 87 91 that that WDT 92 94 is be VBZ 95 106 independent independent JJ 107 109 of of IN 110 115 class class NN 116 118 II ii CD 119 133 transactivator transactivator NN 133 134 . . . 136 144 Patients patient NNS 145 149 with with IN 150 153 one one CD 154 158 type type NN 159 161 of of IN 162 167 major major JJ 168 186 histocompatibility histocompatibility NN 187 194 complex complex NN 195 200 class class NN 201 203 II ii CD 204 212 combined combined JJ 213 229 immunodeficiency immunodeficiency NN 230 234 have have VBP 235 244 mutations mutation NNS 245 247 in in IN 248 249 a a DT 250 254 gene gene NN 255 261 termed term VBN 262 267 class class NN 268 270 II ii CD 271 285 transactivator transactivator NN 286 287 ( ( ( 287 292 CIITA CIITA NNP 292 293 ) ) ) 293 294 , , , 295 300 which which WDT 301 313 coordinately coordinately RB 314 322 controls control VBZ 323 326 the the DT 327 340 transcription transcription NN 341 343 of of IN 344 347 the the DT 348 353 three three CD 354 359 major major JJ 360 365 human human JJ 366 371 class class NN 372 374 II ii CD 375 380 genes gene NNS 380 381 , , , 382 388 HLA-DR HLA-DR NNP 388 389 , , , 390 393 -DQ -DQ NNP 393 394 , , , 395 398 and and CC 399 402 -DP -DP NNP 402 403 . . . 404 411 However however RB 411 412 , , , 413 416 the the DT 417 431 experimentally experimentally RB 432 439 derived derive VBN 440 456 B-lymphoblastoid b-lymphoblastoid JJ 457 461 cell cell NN 462 466 line line NN 466 467 , , , 468 473 clone clone NN 474 476 13 13 CD 476 477 , , , 478 487 expresses express VBZ 488 492 high high JJ 493 499 levels level NNS 500 502 of of IN 503 508 HLADQ HLADQ NNP 509 511 in in IN 512 515 the the DT 516 523 absence absence NN 524 526 of of IN 527 533 HLA-DR HLA-DR NNP 534 537 and and CC 538 544 HLA-DP HLA-DP NNP 544 545 , , , 546 553 despite despite IN 554 557 its its PRP$ 558 565 mapping mapping NN 566 568 by by IN 569 584 complementation complementation NN 585 593 analysis analysis NN 594 596 to to TO 597 601 this this DT 602 607 group group NN 607 608 . . . 609 611 It it PRP 612 615 was be VBD 616 624 possible possible JJ 625 629 that that IN 630 633 one one CD 634 636 of of IN 637 640 the the DT 641 646 clone clone NN 647 649 13 13 CD 650 655 CIITA CIITA NNP 656 663 alleles allele NNS 664 668 bore bear VBD 669 670 a a DT 671 679 mutation mutation NN 680 684 that that WDT 685 692 allowed allow VBD 693 699 HLA-DQ HLA-DQ NNP 699 700 , , , 701 704 but but CC 705 708 not not RB 709 715 HLA-DR HLA-DR NNP 716 718 or or CC 719 722 -DP -DP NNP 723 736 transcription transcription NN 736 737 . . . 738 751 Alternatively alternatively RB 751 752 , , , 753 760 another another DT 761 767 factor factor NN 767 768 , , , 769 777 distinct distinct JJ 778 782 from from IN 783 788 CIITA CIITA NNP 788 789 , , , 790 795 might might MD 796 803 control control VB 804 810 HLA-DQ HLA-DQ NNP 811 821 expression expression NN 821 822 . . . 823 825 We we PRP 826 832 report report VBP 833 837 here here RB 838 842 that that IN 843 850 ectopic ectopic JJ 851 861 expression expression NN 862 864 of of IN 865 870 CIITA CIITA NNP 871 876 cDNAs cdna NNS 877 884 derived derive VBN 885 887 by by IN 888 895 reverse reverse JJ 896 909 transcriptase transcriptase NN 910 920 polymerase polymerase NN 921 926 chain chain NN 927 935 reaction reaction NN 936 940 from from IN 941 946 clone clone NN 947 949 13 13 CD 950 952 do do VBP 953 956 not not RB 957 964 restore restore VB 965 975 expression expression NN 976 978 of of IN 979 985 HLA-DQ HLA-DQ NNP 986 988 in in IN 989 996 another another DT 997 1012 CIITA-deficient ciita-deficient JJ 1013 1017 cell cell NN 1018 1022 line line NN 1022 1023 , , , 1024 1031 RJ2.2.5 RJ2.2.5 NNP 1031 1032 . . . 1033 1035 In in IN 1036 1044 addition addition NN 1044 1045 , , , 1046 1048 no no DT 1049 1054 CIITA CIITA NNP 1055 1062 protein protein NN 1063 1065 is be VBZ 1066 1076 detectable detectable JJ 1077 1079 in in IN 1080 1085 clone clone NN 1086 1088 13 13 CD 1089 1096 nuclear nuclear JJ 1097 1105 extracts extract NNS 1105 1106 . . . 1107 1109 In in IN 1110 1118 contrast contrast NN 1118 1119 , , , 1120 1127 somatic somatic JJ 1128 1132 cell cell NN 1133 1139 fusion fusion NN 1140 1147 between between IN 1148 1153 clone clone NN 1154 1156 13 13 CD 1157 1160 and and CC 1161 1168 RJ2.2.5 rj2.2.5 NN 1169 1177 restored restore VBD 1178 1188 expression expression NN 1189 1191 of of IN 1192 1195 the the DT 1196 1202 HLA-DQ HLA-DQ NNP 1203 1212 haplotype haplotype NN 1213 1220 encoded encode VBN 1221 1223 by by IN 1224 1227 the the DT 1228 1235 RJ2.2.5 RJ2.2.5 NNP 1236 1239 DQB DQB NNP 1240 1244 gene gene NN 1244 1245 . . . 1246 1251 Taken take VBN 1252 1260 together together RB 1260 1261 , , , 1262 1267 these these DT 1268 1272 data datum NNS 1273 1284 demonstrate demonstrate VBP 1285 1288 the the DT 1289 1298 existence existence NN 1299 1301 of of IN 1302 1304 an an DT 1305 1311 HLA-DQ HLA-DQ NNP 1312 1328 isotype-specific isotype-specific JJ 1329 1341 trans-acting trans-acting JJ 1342 1348 factor factor NN 1348 1349 , , , 1350 1355 which which WDT 1356 1365 functions function VBZ 1366 1379 independently independently RB 1380 1382 of of IN 1383 1388 CIITA CIITA NNP 1388 1389 . . .