Immunodominant HIV-1-specific HLA-B- and HLA-C-restricted CD8+ T cells do not differ in polyfunctionality

Virology. 2010 Sep 30;405(2):483-91. doi: 10.1016/j.virol.2010.06.002. Epub 2010 Jul 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Epitopes, T-Lymphocyte
  • HLA-B Antigens
  • HLA-B*58:01 antigen
  • HLA-B57 antigen
  • HLA-C Antigens
  • Immunodominant Epitopes