Jennings S R
J Immunol. 1985 Nov;135(5):3530-6.
Cytotoxic T lymphocytes, generated in C57BL/6 mice in response to herpes simplex virus type 1 (HSV) and known to be restricted in their recognition of HSV-encoded antigen(s) in association with the class I H-2Kb gene product, were consistently found to contain a subpopulation that recognized and lysed uninfected, SV40-transformed cells that expressed the H-2Kbm3 and H-2Kbm11 mutant class I gene products on their cell surface. The mutant cell lines, designated Lgbm3SV and Kbm11SV, share a common amino acid substitution at position 77, with the bm3 mutation having an additional amino acid substitution at position 89. Cross-reactive lysis was observed only after in vivo priming with HSV, suggesting an important role for an antigen-dependent driving step in the expansion of these cross-reactive CTL. The phenotype of the cross-reactive effector population was further confirmed as a T lymphocyte by negative-selection techniques. Limiting dilution analysis of the frequency of cross-reactive CTL precursors suggested that cross-reactivity was mediated by a subpopulation of HSV-specific CTL, and this was confirmed by clonal analysis of the reactivity patterns of short-term, HSV-specific CTL clones. However, analysis of the specificity of the cross-reactive CTL population by cold-target inhibition of bulk culture-derived CTL, or by Spearman ranking analysis of limiting dilution-derived CTL, indicated that the specificity of the cross-reactive population for HSV-infected H-2b target cells and for uninfected bm3 or bm11 target cells was quite distinct. These findings suggested that the cross-reactive CTL population played little, if any, role in the HSV-specific CTL response as measured in vitro. The findings also suggested that the HSV-specific CTL clones able to mediate cross-reactive recognition of the bm3 and bm11 targets had a higher intrinsic avidity for the foreign target than for the inducing antigen.
细胞毒性T淋巴细胞是在C57BL/6小鼠中针对1型单纯疱疹病毒（HSV）产生的，已知其对与I类H-2Kb基因产物相关的HSV编码抗原的识别具有限制性，研究人员一直发现这些细胞毒性T淋巴细胞中含有一个亚群，该亚群能够识别并裂解未感染的、经SV40转化的细胞，这些细胞在其细胞表面表达H-2Kbm3和H-2Kbm11突变I类基因产物。命名为Lgbm3SV和Kbm11SV的突变细胞系在第77位氨基酸处有一个共同的氨基酸替换，而bm3突变在第89位还有一个额外的氨基酸替换。仅在用HSV进行体内致敏后才观察到交叉反应性裂解，这表明抗原依赖性驱动步骤在这些交叉反应性CTL的扩增中起重要作用。通过阴性选择技术进一步证实交叉反应性效应细胞群体的表型为T淋巴细胞。对交叉反应性CTL前体细胞频率的有限稀释分析表明，交叉反应性是由HSV特异性CTL的一个亚群介导的，短期HSV特异性CTL克隆反应模式的克隆分析证实了这一点。然而，通过对大量培养来源的CTL进行冷靶抑制或对有限稀释来源的CTL进行Spearman等级分析来分析交叉反应性CTL群体的特异性，结果表明交叉反应性群体对HSV感染的H-2b靶细胞以及对未感染的bm3或bm11靶细胞的特异性相当不同。这些发现表明，在体外测量时，交叉反应性CTL群体在HSV特异性CTL反应中几乎不起作用（如果有作用的话）。这些发现还表明，能够介导对bm3和bm11靶标的交叉反应性识别的HSV特异性CTL克隆对异源靶标的内在亲和力高于对诱导抗原的亲和力。
