Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala P.O. Box 7072, Uganda.
Department of Immunology and Molecular Biology, College of Health Sciences, Makerere University, Kampala P.O. Box 7072, Uganda.
Int J Mol Sci. 2024 Sep 6;25(17):9683. doi: 10.3390/ijms25179683.
Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8 T cell responses in HIV-1 control, including our recent report of HLA-C03:02 among African children. However, there are no documented optimal HIV-1 CD8 T cell epitopes restricted by HLA-C03:02; additionally, the structural influence of HLA-C03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C03:02 CD8 T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope potentially restricted to HLA-C03:02. Residues E62, T142, and E151 in the HLA-C03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.
尽管人们一直在努力研制有效的 HIV-1 疫苗，但至今仍未成功。越来越多的证据表明，HLA-C 限制性 CD8 T 细胞应答在 HIV-1 控制中可能发挥作用，包括我们最近在非洲儿童中报告的 HLA-C03:02。然而，目前尚无文献记载的受 HLA-C03:02 限制的最佳 HIV-1 CD8 T 细胞表位；此外，HLA-C03:02 对表位结合的结构影响尚不确定。免疫信息学方法为发现 HLA 限制性表位提供了一种快速且经济的方法。在这里，我们采用免疫肽组学来鉴定 HLA-C03:02 CD8 T 细胞表位。我们鉴定了一个潜在受 HLA-C03:02 限制的 clade 特异性 Gag 衍生 GY9 (GTEELRSLY) HIV-1 p17 基质表位。HLA-C03:02 结合槽中的残基 E62、T142 和 E151 以及 GY9 表位上的位置 p3、p6 和 p9 对于塑造和稳定表位结合至关重要。我们的发现支持 HLA-C 分子对 HIV-1 控制的贡献不断增加的证据，并为疫苗策略提供了前景。
