Background:  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 viral load is being reduced, suggesting that circulating viruses may lack immunodominant epitopes targeted through HLA-A2.

Methods:  A total of 88 HLA-A2⁺ individuals (14 with primary infection and 74 with chronic infection) were enrolled in this study. Autologous viral sequences were determined from PBMC or plasma and HIV-1-specific CD8⁺ T-cell responses were quantified using an IFN-g ELISpot assay. Epitope-specific CD8⁺ T-cell clones were generated using limiting dilution techniques, and recognition of consensus sequence epitopes and variant epitopes was compared using serial dilution of epitope peptides. 

Results:  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 acutely infected with viruses containing the most common current sequence within this epitope (consensus sequence) could not 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-A*0201 and was recognized by epitope-specific T cells at lower peptide concentrations than the consensus sequence epitope.

Conclusions:  These data demonstrate that HLA-A2 is capable of contributing to the acute phase CTL 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.

Keywords: CD8+ T cells; clade B consensus sequence; immunogenicity