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HIV-1 specific HLA-B-restricted CD8+ T cell responses differ from HLA-C-restricted responses in antiviral effectiveness. To investigate possible reasons for these differences, we characterized the frequency and polyfunctionality of immmunodominant HLA-B*57/B5801- and HLA-Cw*07-restricted CD8+ T cells occurring concurrently in nine study subjects assessing IFN-gamma, TNF-alpha, IL-2, MIP-1beta, and CD107a by flow cytometry and analyzed sequence variation in targeted epitopes. HLA-B*57/5801 and HLA-Cw*07 restricted CD8+ T cells did not differ significantly in polyfunctionality (p=0.84). Possession of three or more functions correlated positively with CD4+ T cell counts (r=0.85; p=0.006) and monofunctional CD8+ T cells inversely correlated with CD4 cell counts (r=-0.79; p=0.05). There were no differences in polyfunctionality of CD8+ T cells specific to wildtype versus mutated epitopes. These results suggest that loss of polyfunctionality and increase in monofunctional HIV-1-specific CD8+ T cells are associated with disease progression independent of restricting HLA allele. Furthermore, sequence variation does not appear to significantly impact CD8+ T cell polyfunctionality in chronic HIV-1 infection.

Original publication

DOI

10.1016/j.virol.2010.06.002

Type

Journal

Virology

Publication Date

30/09/2010

Volume

405

Pages

483 - 491

Keywords

Adult, Amino Acid Sequence, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes, Chronic Disease, Epitopes, T-Lymphocyte, Female, HIV Infections, HIV-1, HLA-B Antigens, HLA-C Antigens, Humans, Immunodominant Epitopes, Male, Middle Aged, Molecular Sequence Data, Mutation, Viral Load