In:
Journal of Virology, American Society for Microbiology, Vol. 79, No. 8 ( 2005-04-15), p. 5000-5005
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 (Vpr 59-67 ) 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 I 60 L variant all developed these responses. The I 60 L 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.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.79.8.5000-5005.2005
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2005
detail.hit.zdb_id:
1495529-5
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