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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

2004; Wiley; Volume: 35; Issue: 1 Linguagem: Inglês

10.1002/eji.200425487

1521-4141

Christine A. Jansen, Stefan Kostense, Kristin Vandenberghe, Nening M. Nanlohy, Iris M. De Cuyper, Erwan Piriou, Erik H. Manting, Frank Miedema, Debbie van Baarle,

T-cell and B-cell Immunology

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-gamma 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.