Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV
disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid
disease progression.
HLA-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated
disease progression in B-clade
infection. This study investigates the observation that
HLA-B*07:02 is not associated with a high viral setpoint in C-clade
infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8(+)
T cell epitopes. We observed that C-clade-infected individuals with
HLA-B*07:02 target a broader range of Gag
epitopes, and to higher magnitudes, than do individuals infected with B-clade
infection. In particular, a novel p17-Gag (Gag22-30, RPGGKKHYM)
epitope is targeted in >50% of
HLA-B*07:02-positive C-clade-infected individuals but clade-specific differences in this
epitope result in nonimmunogenicity in B-clade
infection. Only the C-clade p24-Gag "GL9" (Gag355-363, GPSHKARVL)
epitope-specific CD8(+) T cell response out of 16 studied was associated with a low viral setpoint. Although this
epitope was also targeted in B-clade
infection, the escape mutant S357S is present at higher frequency in B-clade
infection than in C-clade
infection (70% versus 43% in
HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed.