The majority of currently circulating human immunodeficiency virus type 1 clade B viruses fail to prime cytotoxic T-lymphocyte responses against an otherwise immunodominant HLA-A2-restricted epitope: implications for vaccine design

J Virol. 2005 Apr;79(8):5000-5. doi: 10.1128/JVI.79.8.5000-5005.2005.

Abstract

Human immunodeficiency virus type 1 (HIV-1) mutates to escape immune selection pressure, but there is little evidence of selection mediated through HLA-A2, the dominant class I allele in persons infected with clade B virus. Moreover, HLA-A2-restricted responses are largely absent in the acute phase of infection as the viral load is being reduced, suggesting that circulating viruses may lack immunodominant epitopes targeted through HLA-A2. Here we demonstrate an A2-restricted epitope within Vpr (Vpr59-67) that is targeted by acute-phase HIV-1-specific CD8+ T cells, but only in a subset of persons expressing HLA-A2. Individuals in the acute stage of infection with viruses containing the most common current sequence within this epitope (consensus sequence) were unable to mount epitope-specific T-cell responses, whereas subjects infected with the less frequent I60L variant all developed these responses. The I60L variant epitope was a stronger binder to HLA-A2 and was recognized by epitope-specific T cells at lower peptide concentrations than the consensus sequence epitope. These data demonstrate that HLA-A2 is capable of contributing to the acute-phase cytotoxic T-lymphocyte response in infected subjects, but that most currently circulating viruses lack a dominant immunogenic epitope presented by this allele, and suggest that immunodominant epitopes restricted by common HLA alleles may be lost as the epidemic matures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Vaccines*
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / virology
  • Amino Acid Sequence
  • Conserved Sequence
  • Drug Design*
  • Epitopes / immunology
  • Gene Products, vpr / chemistry
  • Gene Products, vpr / immunology
  • HIV-1 / classification
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HLA-A2 Antigen / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Interferon-gamma / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology
  • vpr Gene Products, Human Immunodeficiency Virus

Substances

  • AIDS Vaccines
  • Epitopes
  • Gene Products, vpr
  • HLA-A2 Antigen
  • Histocompatibility Antigens Class I
  • vpr Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma