Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein.

Kyobe, Samuel; Mwesigwa, Savannah; Nkurunungi, Gyaviira; Retshabile, Gaone; Egesa, Moses; Katagirya, Eric; Amujal, Marion; Mlotshwa, Busisiwe C; Williams, Lesedi; Sendagire, Hakim; +7 more... On Behalf Of The CAfGEN Consortium; Kiragga, Dithan; Mardon, Graeme; Matshaba, Mogomotsi; Hanchard, Neil A; Kyosiimire-Lugemwa, Jacqueline; Robinson, David; (2024) Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein. International journal of molecular sciences, 25 (17). p. 9683. ISSN 1422-0067 DOI: https://doi.org/10.3390/ijms25179683

Abstract

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-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 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-C*03:02 CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope potentially restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 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.

Additional Information

Item Type	Article
Faculty and Department	MRC Uganda > UG-Basic Science MRC Uganda > UG-HIV Care
PubMed ID	39273630
Elements ID	229239
Official URL	http://dx.doi.org/10.3390/ijms25179683