Genetic control of specific immune suppression. III. Mapping of H-2 complex complementing genes controlling immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).
Genetic control of specific immune suppression. III. Mapping of H-2 complex complementing genes controlling immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).
复制标题
特异性免疫抑制的遗传控制。 iii。 H-2复合物补充基因控制免疫抑制的基因，由随机共聚物L-谷氨酸50-L-酪氨酸50（GT）的映射。
DOI：
10.1084/jem.144.1.272
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发表时间：
1976-07-01
影响因子：
15.3
通讯作者：
Benacerraf, B
中科院分区：
文献类型：
--
作者：
Debre, P;Waltenbaugh, C;Dorf, M;Benacerraf, B
我们实验室的早期研究表明，L-谷氨酸、L-丙氨酸和L-酪氨酸（GAT）的结合刺激T细胞的发育，T细胞能够特异性抑制体内和体外无应答菌株（携带H-2（s）、H-2（q）和H-2（p）单倍型）对与免疫原性载体甲基化牛血清白蛋白MBSA复合的GAT的抗体应答（1，2）。然后，我们将这些发现扩展到另一种抗原，L-谷氨酸和L-酪氨酸（GT）的共聚物。19个近交系或同类系抗性小鼠品系在用该合成多肽在佐剂中免疫后均未产生对GT的抗体应答。然而，研究的所有菌株均对GT与MBSA复合物产生IgG空斑形成细胞（PFC）初级应答（3）。这使我们能够确定：（a）GT预免疫抑制某些但不是所有菌株对GT-MBSA的反应;（B）这种抑制可以通过GT致敏动物的胸腺细胞和脾细胞转移;（c）GT特异性抑制细胞的发育受H-2连锁基因的显性控制，这些基因被称为特异性免疫抑制基因（Is基因）;（d）Is基因具有抗原特异性，因为在携带H-2（q）单倍型的菌株中，GAT-MBSA反应被GAT抑制，而在这些相同的菌株中，GT-MBSA反应不被相关聚合物GT抑制（3，4）。本研究中报道的实验映射了负责H-2复合物内GT特异性抑制的Is基因。这些数据表明，K和D基因座不涉及GT特异性抑制，并且这种现象是由互补或相互作用的基因控制的，这些基因映射在IB和IC亚区之间的交叉事件的两侧。
Earlier studies from our laboratory demonstrated that the terpolymer of L-glutamic acid, L-alanine, and L-tyrpsine (GAT) stimulated the development of T cells capable of specifically suppressing the antibody responses in vivo and in vitro of nonresponder strains (bearing the H-2(s), H-2(q), and H-2(p) haplotypes) to GAT complexed with an immunogenic carrier, methylated bovine serum albumin, MBSA (1,2). We then extended these findings to another antigen, the copolymer of L-glutamic acid and L-tyrosine (GT). None of 19 inbred or congenic resistant mouse strains developed antibody responses to GT after immunization with this synthetic polypeptide in adjuvants. All the strains investigated, however, developed IgG plaque-forming cells (PFC) primary responses to GT complexed with MBSA (3). This permitted us to determine that: (a) preimmunization with GT suppressed the response to GT-MBSA in certain but not in all strains; (b) the suppression could be transferred by thymocytes and spleen cells from GT-primed animals; (c) the development of GT-specific suppressor cells is under dominant control of H-2- linked gene(s) which have been designated specific immune suppressor genes (Is genes); (d) the Is genes are antigen specific since GAT-MBSA responses are suppressed by GAT in strains carrying the H-2(q) haplotype, while GT-MBSA responses are not suppressed by the related polymer GT in these same strains (3,4). The experiments reported in this study map the Is genes responsible for GT-specific suppression within the H-2 complex. The data indicate that the K and D loci are not concerned with GT-specific suppression, and that this phenomenon is controlled by complementing or interacting genes which map on either side of cross-over events between the IB and IC subregions.