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T-cell receptor (TCR) diversity of virus-specific CD8⁺ T cells likely helps prevent escape mutations in chronic viral infections. To understand the dynamics of the virus-specific T cells in more detail, we followed the evolution of the TCR repertoire specific for a dominant HLA-B*08–restricted epitope in Nef (FLKEKGGL) in a cohort of subjects infected with HIV. Epitope-specific CD8⁺ T cells used structurally diverse TCR repertoires, with different TCRβ variable regions and with high amino acid diversity within antigen recognition sites. In a longitudinal study, distinct Vβ populations within the HIV-specific TCR repertoire expanded simultaneously with changes in plasma viremia, whereas other Vβ populations remained stable or even decreased. Despite antigenic variation in some subjects, all subjects had the consensus sequence present during the study period. Functional analysis of distinct Vβ populations revealed …