Human immunodeficiency virus (HIV) or AIDS is currently the leading cause of death in Uganda, with at least three HIV clades (subtypes) accounting for most new infections. Whether an effective vaccine formulated on viruses from a single clade will be able to protect against infection from other local clades remains unresolved. We examined the T-cell immune responses from a cohort of HIV-seropositive individuals in Uganda with predominantly clade A and D infections. Surprisingly, we observed similar frequencies of cross-clade T-cell responses to the gag, env, and nef regions. Our data suggest that the level of viral sequence variability between distinct HIV strains does not predict the degree of cross-clade responses. High sequence homologies were also observed between consensus peptides and sequences from viral isolates, supporting the use of consensus amino acid sequences to identify immunogenic regions in studies of large populations.Human immunodeficiency virus (HIV) or AIDS continues to be the leading cause of death in sub-Saharan Africa. Although there is a critical need for an effective HIV vaccine, the undefined correlates of protective immunity in HIV type 1 (HIV-1) infection remain an important obstacle. Nevertheless, a wealth of evidence suggests that a robust cellular immune response may curtail viral replication; therefore, HIV vaccine designs have, to date, focused on eliciting strong cellular immune responses.T-cell epitope recognition is dependent on the individual class I human leukocyte antigen (HLA) alleles. The pattern of antigen recognition and immunodominance may be driven by the prevalence of these alleles in the studied population (19). The identification of highly immunogenic and conserved regions is also complicated by HIV sequence diversity (8). T-cell responses against HIV can, in turn, influence the HIV populations in generating immune escape viral variants (33).There is comprehensive data on T-cell epitopes for HIVinfected individuals of Caucasian descent. However, there is a relative paucity of information for the geographic regions where the HIV epidemic is spreading the fastest at this time, particularly sub-Saharan Africa (1,2,7,34,35). In Uganda, clades A and D (as well as A/D recombinant strains) are responsible for approximately 95% of HIV-1 infections (3,11,22,23). Previous studies of HIV-1-specific cellular immune responses in small cohorts of HIV-infected individuals and vaccine recipients in Uganda have shown cross-clade immune recognition (5, 6, 31). Nevertheless, the issue of whether an effective vaccine formulated on viruses from a single clade could protect equally well against viruses from other local clades remains unresolved.We evaluated the pattern of T-cell antigen recognition in the context of the HLA alleles and multiple circulating HIV subtypes in a cross-sectional study of HIV-infected Ugandan adults. We investigated factors that determine cross-clade Tcell recognition in the context of vaccine design for Uganda and sub-Saharan Africa. MATERIALS AND METHODS St...

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