Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Eur J Immunol. 2012 Oct;42(10):2621-31. doi: 10.1002/eji.201242483. Epub 2012 Aug 6.
It is known that overlapping HIV-1 peptides of different lengths can be presented by a given HLA class I molecule. However, the role of those peptides in CD8(+) T cells recognition of HIV-1-infected cells remains unclear. Here we investigated the recognition of overlapping 8-mer to 11-mer peptides of Pol 155-165 by HLA-B54:01-restricted CD8(+) T cells. The analysis of ex vivo T cells using ELISPOT and tetramer binding assays showed that there were different patterns of CD8(+) T-cell responses to these peptides among chronically HIV-1-infected HLA-B54:01(+) individuals, though the response to the 9-mer peptide was the strongest among them. CD8(+) T-cell clones with TCRs specific for the 9-mer, 10-mer, and/or 11-mer peptides effectively killed HIV-1-infected cells. Together, these results suggest that the 9-mer and 10-mer peptides could be predominantly presented by HLA-B*54:01, though it remains possible that the 11-mer peptide was also presented by this HLA allele. The present study demonstrates effective CD8(+) T-cell recognition of HIV-1-infected cells via presentation of multiple overlapping HIV-1 peptides and cross-recognition by the CD8(+) T cells.
已知不同长度的重叠 HIV-1 肽段可由特定的 HLA Ⅰ类分子呈递。然而,这些肽段在 CD8+T 细胞识别 HIV-1 感染细胞中的作用仍不清楚。在这里,我们研究了 HLA-B54:01 限制性 CD8+T 细胞对 Pol 155-165 的重叠 8 -mer 至 11-mer 肽的识别。使用 ELISPOT 和四聚体结合测定法对体外 T 细胞进行分析表明,在慢性 HIV-1 感染的 HLA-B54:01(+)个体中,这些肽段的 CD8+T 细胞反应存在不同模式,尽管其中 9- 肽的反应最强。针对 9- 肽、10- 肽和/或 11- 肽的 TCR 特异性 CD8+T 细胞克隆有效地杀伤了 HIV-1 感染的细胞。综上所述,这些结果表明 9- 肽和 10- 肽可能主要由 HLA-B*54:01 呈递,尽管 11- 肽也可能由该 HLA 等位基因呈递。本研究表明,通过呈递多个重叠的 HIV-1 肽段和 CD8+T 细胞的交叉识别,可以有效识别 HIV-1 感染的细胞。