With the knowledge of each individual��s HLA alleles and the regions of Gag they responded to, we could determine the HLArestriction of the vast Y-27632 dihydrochloride majority of responses using data from the Los Alamos National Database. Subjects who expressed the HLAB* 57 or B*42 alleles were more likely to restrict their highest magnitude responses through peptides with known B*57 and B*42 epitopes suggesting a strong contribution of these alleles to immunodominance. In addition, such responses made up the great majority of the total Gag-specific response in these individuals . Eight subjects in this cohort expressed at least one HLA-B*42 allele and all eight restricted their immunodominant response through this allele . B*42 restricted responses accounted for an average of 69% of the total observed Gagspecific response in these individuals. Similarly, five subjects expressed at least one HLA- B*57 allele and again, all 5 of these subjects had an immunodominant response restricted through B*57. In these subjects, B*57 restricted responses accounted for, on average, 84% of their total observed Gag-specific response. Several studies have suggested that qualitative characteristics of the HIV-1-specific CD8+ T cell response are associated with viral control and disease progression . Other studies have suggested that immunodominance patterns of HIV-1-specific CD8+ T cell responses are of great importance in establishing control of the virus and HIV-1 disease . We observed no difference in the magnitude or breadth of the Gagspecific CD8+ T cell response between the two groups, as measured by IFN-c production, consistent with other studies . In contrast, there were several differences in the epitope regions of Gag that were targeted by CD8+ T cell responses. In bulk CD8+ T cell populations we observed a significantly higher frequency of na?��ve CD8+ T cells in the NS subjects compared to the SS subjects, but no differences in any other CD8+ T cell subsets. The differentiation INC280 c-Met inhibitor profiles and multifunctional capacity of Gag-specific CD8+ T cells, regardless of immunodominance, were similar between the progression groups. Together, these data suggest that, at least in perinatally infected adolescents, the region of Gag targeted by CD8+ T cells may have more importance to the rate of disease progression than qualitative features such as differentiation and multifunctionality.