Sewell A K, Harcourt G C, Goulder P J, Price D A, Phillips R E
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, GB.
Eur J Immunol. 1997 Sep;27(9):2323-9. doi: 10.1002/eji.1830270929.
Mutations in human immunodeficiency virus (HIV) cluster in cytotoxic T lymphocyte (CTL) epitopes (Phillips, R. E. et al., Nature 1991. 354: 453) and are subject to immune-mediated positive selection (Price, D. A. et al., Proc. Natl. Acad. Sci. USA 1997. 94: 1890). We studied the effects of naturally occurring mutations in the HIV-1 p17 Gag HLA A2 restricted epitope SLYNTVATL on recognition by anti-HIV CTL. Most of these naturally occurring mutants escaped killing by one CTL line and the majority acted as CTL antagonists. We also investigated whether CTL exposed to a strict antagonist peptide restricted by HLA A2 were unresponsive when exposed to targets presenting the wild-type sequence. The results show that antagonism of anti-HIV CTL killing requires the simultaneous presence of agonist and antagonist peptide. We found no evidence that CTL exposed to an antagonist received a functionally negative signal since these CTL retained an unimpaired capacity to lyse targets bearing wild-type peptide.
人类免疫缺陷病毒（HIV）的突变聚集在细胞毒性T淋巴细胞（CTL）表位中（菲利普斯，R.E.等人，《自然》1991年。354:453），并受到免疫介导的正选择（普赖斯，D.A.等人，《美国国家科学院院刊》1997年。94:1890）。我们研究了HIV-1 p17 Gag HLA A2限制性表位SLYNTVATL中自然发生的突变对抗HIV CTL识别的影响。这些自然发生的突变体大多逃脱了一条CTL系的杀伤，且大多数起到CTL拮抗剂的作用。我们还研究了暴露于受HLA A2限制的严格拮抗剂肽的CTL在暴露于呈现野生型序列的靶标时是否无反应。结果表明，抗HIV CTL杀伤的拮抗作用需要激动剂肽和拮抗剂肽同时存在。我们没有发现证据表明暴露于拮抗剂的CTL接收到功能上的负信号，因为这些CTL保留了裂解携带野生型肽的靶标的未受损能力。
