Byrne J A, Ahmed R, Oldstone M B
J Immunol. 1984 Jul;133(1):433-9.
Cytotoxic T lymphocytes (CTL) were induced in C57BL/6 and (C57BL/6 X DBA/2)F1 mice after immunization with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV-Arm) and were cloned by limiting dilution in vitro. The cytotoxic activity of these clones was LCMV specific and H-2 restricted. All clones induced in C57BL/6 (H-2b) mice with LCMV-Arm lysed target cells infected with each of five distinct strains of LCMV (Arm, Traub , WE, Pasteur, and UBC ), suggesting recognition of common regions of viral proteins in association with H-2b molecules. In contrast, one clone obtained from (B6 X D2)F1 mice and restricted to the H-2d haplotype only lysed cells infected with one of three strains of virus (Arm, Traub , WE) but not two others (Pasteur, UBC ), suggesting recognition of variable regions of viral proteins in the context of H-2d molecules. To assess the fine specificity for H-2 molecules, we tested H-2Kb-restricted CTL clones for their ability to kill LCMV-infected target cells bearing mutations in their H-2Kb, and we tested clones presumed to be restricted to the H-2Db region for their ability to all LCMV targets cells bearing a mutation in the H-2Db region. Several different patterns of killing of the mutant targets were observed, indicating that a number of different epitopes on the H-2b molecules were used as restricting determinants for LCMV antigen recognition by CTL. Thus, cross-reactive viral determinants were recognized in the context of several different restricting determinants. Mutations in the N or C1 domains of the H-2 molecule affected recognition by a single LCMV specific CTL clone. One implication of this result is that CTL recognize a conformational determinant on the H-2 molecule formed by the association of virus antigen(s) with H-2. An alternate explanation is that one site on the H-2 molecule is involved in the interaction of viral antigens with H-2, whereas another may serve as a binding site for the CTL receptor.
用淋巴细胞性脉络丛脑膜炎病毒阿姆斯特朗株（LCMV-Arm）免疫C57BL/6和（C57BL/6×DBA/2）F1小鼠后诱导出细胞毒性T淋巴细胞（CTL），并通过体外有限稀释法进行克隆。这些克隆的细胞毒性活性具有LCMV特异性且受H-2限制。用LCMV-Arm在C57BL/6（H-2b）小鼠中诱导出的所有克隆均裂解了被五种不同LCMV毒株（Arm、Traub、WE、巴斯德株和UBC）中的每一种感染的靶细胞，这表明与H-2b分子相关联的病毒蛋白共同区域被识别。相比之下，从（B6×D2）F1小鼠获得且仅受H-2d单倍型限制的一个克隆仅裂解了被三种病毒毒株（Arm、Traub、WE）之一感染的细胞，而未裂解另外两种（巴斯德株、UBC）感染的细胞，这表明在H-2d分子背景下病毒蛋白可变区域被识别。为了评估对H-2分子的精细特异性，我们测试了受H-2Kb限制的CTL克隆对杀伤其H-2Kb带有突变的LCMV感染靶细胞的能力，并且测试了推测受H-2Db区域限制的克隆对杀伤H-2Db区域带有突变的所有LCMV靶细胞的能力。观察到对突变靶细胞的几种不同杀伤模式，表明H-2b分子上的许多不同表位被用作CTL识别LCMV抗原的限制决定簇。因此，在几种不同的限制决定簇背景下识别了交叉反应性病毒决定簇。H-2分子的N或C1结构域中的突变影响单个LCMV特异性CTL克隆的识别。该结果的一个含义是CTL识别由病毒抗原与H-2结合形成的H-2分子上的构象决定簇。另一种解释是H-2分子上的一个位点参与病毒抗原与H-2的相互作用，而另一个位点可能作为CTL受体的结合位点。
