1. Impact of micropolymorphism outside the 1 peptide binding groove in the clinically-relevant allele HLA-C*14 on T cell responses in HIV-1 infection
- Author
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Chikata, T, Paes, W, Kuse, N, Partridge, T, Ternette, N, Borrow, P, and Takiguchi, M
- Abstract
There is increasing evidence for the importance of HLA-C-restricted CD8+ 28 T-cells in HIV-1 control, but these responses are relatively poorly investigated. Numbers of HLA-C-restricted HIV-1 epitopes identified are much smaller than those of HLA-A-restricted or HLA-B-restricted ones. Here, we utilized a mass spectrometry-based approach to identify HIV-1 peptides presented by HLA-C*14:03 protective and HLA-C*14:02 non-protective alleles. We identified twenty-five 8-11mer HLA-I-bound HIV-1 peptides from HIV-1-infected HLA-C*14:02+ /14:03+ 34 cells. Analysis of T-cell responses to these peptides identified novel 6 T-cell epitopes targeted in HIV-1-infected HLA-C*14:02+ /14:03+ subjects. Analyses using HLA-stabilization assays demonstrated that all 6 epitope peptides exhibited higher binding to and greater cell-surface stabilization of HLA-C*14:02 than HLA-C*14:03. T-cell response magnitudes were typically higher in HLA-C*14:02+ than HLA-C*14:03+ individuals,with responses to the Pol KM9 and Nef epitopes being significantly higher. The results show that HLA-C*14:02 can elicit stronger T cell responses to HIV-1 than HLA-C*14:03 and suggest that the single amino acid difference between these HLA-C14 subtypes at position 21, outside the peptide-binding groove, indirectly influences the stability of peptide-HLA-C*14 complexes and induction/expansion of HIV-specific T-cells. Taken together with a previous finding that KIR2DL2+ NK cells recognized HLA-C*14:03+ HIV-1-infected cells more than HLA-C*14:02+ one, the present study indicates that these HLA-C*14 subtypes differentially impact on HIV-1 control by T-cells and NK cells.
- Published
- 2022