Genetic control of T cell responsiveness to the Friend murine leukemia virus envelope antigen. Identification of class II loci of the H-2 as immune response genes.
Genetic control of T cell responsiveness to the Friend murine leukemia virus envelope antigen. Identification of class II loci of the H-2 as immune response genes.
复制标题
DOI：
10.1084/jem.168.5.1587
复制
发表时间：
1988-11-01
期刊：
影响因子：
--
通讯作者：
Chesebro B
中科院分区：
文献类型：
--
作者：
Miyazawa M;Nishio J;Chesebro B
用表达Friend小鼠白血病辅助病毒（F-MuLV）全env基因的重组痘苗病毒免疫小鼠，制备了特异性转染F-MuLV包膜糖蛋白的T细胞。当抗原脉冲腹膜渗出细胞（PEC）在H-2的K、A β、A α和E β位点上具有b等位基因刺激T细胞时，观察到F-MuLV包膜特异性H-2a/b T细胞的显著增殖反应。另一方面，PEC在这些位点上只有kappa等位基因，即使PEC在E α、S或D位点上有b等位基因，也不会诱导包膜特异性T细胞增殖。抗原脉冲刺激下H-2a/b T细胞的F-MuLV包膜特异性增殖，H-2a/b PEC被抗i- ab和抗i- Ek单抗特异性阻断，而不被抗kb、抗kk或抗i- ak单抗特异性阻断。此外,(B10。MBR x A/WySn)F1小鼠仅在K位点有b等位基因，而在I-A亚区没有b等位基因，对包膜糖蛋白无应答，A β位点的bm12突变完全消除了T细胞对该抗原的应答性。这些结果表明，增殖性T细胞在I- ab、杂交I-Ak /b和/或杂交I- ek /b II类MHC分子背景下识别F-MuLV包膜蛋白上有限数量的表位，但在I-Ak或I- ek分子背景下无法识别相同的包膜蛋白。H-2I区对T细胞包膜糖蛋白识别的影响似乎控制了牛痘- f - mulv env疫苗免疫后对Friend病毒复合物的体内保护性免疫诱导。因此，这些结果首次为Ir基因控制的应答/非应答表型影响小鼠对致病性病毒的免疫应答提供了直接证据。
T cells primed specifically for the envelope glycoprotein of Friend murine leukemia helper virus (F-MuLV) were prepared by immunizing mice with a recombinant vaccinia virus that expressed the entire env gene of F-MuLV. Significant proliferative responses of F-MuLV envelope- specific, H-2a/b T cells were observed when the T cells were stimulated with antigen-pulsed peritoneal exudate cells (PEC) having the b allele at the K, A beta, A alpha, and E beta loci of the H-2. On the other hand, PEC having only the kappa allele at these loci did not induce the envelope-specific T cell proliferation, even when the PEC had the b allele at the E alpha, S, or D loci. F-MuLV envelope-specific proliferation of H-2a/b T cells under the stimulation of antigen- pulsed, H-2a/b PEC was specifically blocked with anti-I-Ab and anti-I- Ek mAbs but not with anti-Kb, anti-Kk, or anti-I-Ak mAbs. Moreover, (B10.MBR x A/WySn)F1 mice that have the b allele only at the K locus but not in I-A subregion were nonresponders to the envelope glycoprotein, and the bm12 mutation at the A beta locus completely abolished the T cell responsiveness to this antigen. These results indicate that proliferative T cells recognize a limited number of epitopes on F-MuLV envelope protein in the context of I-Ab, hybrid I- Ak/b, and/or hybrid I-Ek/b class II MHC molecules but fail to recognize the same envelope protein in the context of I-Ak or I-Ek molecules. This influence of the H-2I region on T cell recognition of the envelope glycoprotein appeared to control in vivo induction of protective immunity against Friend virus complex after immunization with the vaccinia-F-MuLV env vaccine. Thus, these results provide, for the first time, direct evidence for Ir gene-controlled responder/nonresponder phenotypes influencing the immune response to a pathogenic virus of mice.