Recognition of two overlapping CTL epitopes in HIV-1 p17 by CTL from a long-term nonprogressing HIV-1-infected individual.
Recognition of two overlapping CTL epitopes in HIV-1 p17 by CTL from a long-term nonprogressing HIV-1-infected individual.
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DOI：
10.4049/jimmunol.161.9.4875
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发表时间：
1998-11
影响因子：
4.4
通讯作者：
T. Harrer;E. Harrer;P. Barbosa;F. Kaufmann;R. Wagner;S. Brüggemann;J. Kalden;M. Feinberg;R. Johnson;S. Buchbinder;B. Walker
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文献类型：
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作者：
T. Harrer;E. Harrer;P. Barbosa;F. Kaufmann;R. Wagner;S. Brüggemann;J. Kalden;M. Feinberg;R. Johnson;S. Buchbinder;B. Walker
HIV-1感染已被证明在一些感染者中能引起强烈的CTL反应，但关于靶表位与体内病毒准种之间的关系的数据很少。在这项研究中，我们检测了一名感染15年的患者的CTL反应，患者的CD4计数持续为500个/微升。在体内激活的CTL反应主要针对p17区域的两个重叠的Gag CTL表位，该区域是病毒复制的关键区域。9-聚体SLYNTVATL(氨基酸77-85)与人类白细胞抗原A2结合，而重叠的8-聚体TLYCVHQR(氨基酸83-91)被人类白细胞抗原A11限制性CTL识别。对PBMC和血浆中病毒的体内序列分析表明，该区域存在序列变异，这并不影响病毒的体外复制，但减少了对A11限制性CTL反应的识别，并维持了A2限制性反应。这些结果表明，p17蛋白的一个重要区域可以通过两个不同的HLA分子同时被CTL靶向，并且可以在不损害病毒复制的情况下发生免疫逃避CTL识别。此外，他们还证明，抗原处理可以允许在同一感染细胞中呈现重叠的表位，这可能会受到序列变异的截然不同的影响。
HIV-1 infection has been shown to elicit strong CTL responses in some infected persons, but few data are available regarding the relationship between targeted epitopes and in vivo viral quasispecies. In this study, we examined the CTL response in a person infected for 15 yr with a CD4 count persistently >500 cells/microl. The dominant in vivo activated CTL response was directed against two overlapping Gag CTL epitopes in an area of p17 known to be essential for viral replication. The 9-mer SLYNTVATL (amino acids 77-85) was recognized in conjunction with HLA-A2, whereas the overlapping 8-mer TLYCVHQR (amino acids 83-91) was recognized by HLA-A11-restricted CTL. Analysis of in vivo virus sequences both in PBMC and plasma revealed the existence of sequence variation in this region, which did not affect viral replication in vitro, but decreased recognition by the A11-restricted CTL response, with maintenance of the A2-restricted response. These results indicate that an essential region of the p17 protein can be simultaneously targeted by CTL through two different HLA molecules, and that immune escape from CTL recognition can occur without impairing viral replication. In addition, they demonstrate that Ag processing can allow for presentation of overlapping epitopes in the same infected cell, which can be affected quite differently by sequence variation.