High responsiveness of HLA‐B57‐restricted Gag‐specific CD8+ T cells in vitro may contribute to the protective effect of HLA‐B57 in HIV‐infection

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Abstract
HLA‐B57 has been shown to be associated with long‐term asymptomatic HIV‐1 infection. To investigate the biological mechanism by which the HLA‐B57 allele could protect from HIV‐1 disease, we studied both the number of CD8+ T cells as well as CD8+ T cell responsiveness directed to different HIV‐1 Gag peptides presented by HLA‐A2, ‐B8 or ‐B57. T cells specific for the HLA‐B57 peptide KAFSPEVIPMF responded more readily and to a higher extend to antigenic stimulation in vitro than T cells specific for the HLA‐A2 peptide SLYNTVATL or the HLA‐B8 peptide EIYKRWII. This phenomenon was reproducible with T cells from individuals expressing HLA‐B57 in combination with one or both of the other alleles and was persistent during long‐term follow‐up. Lower reactivity of A2‐ and B8‐restricted T cells was not explained by mutations in the B8‐ or A2‐restricted Gag‐peptides. Moreover, no correlation between peptide mutation frequency and IFN‐γ production by the corresponding Gag‐specific T cells was observed. In conclusion, functional differences were observed between T cells specific for HIV epitopes derived from the same protein presented by different HLA molecules. B57‐restricted KAFSPEVIPMF‐specific CD8+ T cells have relatively high responsiveness, which could contribute to the protective effect of HLA‐B57 in HIV infection.