Debré P, Waltenbaugh C, Dorf M, Benacerraf B
J Exp Med. 1976 Jul 1;144(1):272-6. doi: 10.1084/jem.144.1.272.
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.
我们实验室早期的研究表明,L-谷氨酸、L-丙氨酸和L-色氨酸的三元共聚物(GAT)能刺激T细胞的发育,这些T细胞能够特异性抑制无反应株(携带H-2(s)、H-2(q)和H-2(p)单倍型)在体内和体外对与免疫原性载体甲基化牛血清白蛋白(MBSA)复合的GAT的抗体反应(1,2)。然后,我们将这些发现扩展到另一种抗原,即L-谷氨酸和L-酪氨酸的共聚物(GT)。在用这种合成多肽在佐剂中免疫后,19种近交或同源抗性小鼠品系中没有一个对GT产生抗体反应。然而,所有研究的品系都对与MBSA复合的GT产生了IgG斑块形成细胞(PFC)初级反应(3)。这使我们能够确定:(a)用GT预免疫在某些但不是所有品系中抑制了对GT-MBSA的反应;(b)这种抑制可以由来自GT预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,这些基因已被指定为特异性免疫抑制基因(Is基因);(d)Is基因是抗原特异性的,因为在携带H-2(q)单倍型的品系中,GAT-MBSA反应被GAT抑制,而在这些相同品系中,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将负责GT特异性抑制的Is基因定位在H-2复合体内。数据表明,K和D位点与GT特异性抑制无关,并且这种现象由位于IB和IC亚区域之间交叉事件两侧的互补或相互作用基因控制。