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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.

Original publication

DOI

10.1128/JVI.79.8.5000-5005.2005

Type

Journal

J Virol

Publication Date

04/2005

Volume

79

Pages

5000 - 5005

Keywords

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