The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8⁺ T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK_263-272) presented by human leukocyte antigen (HLA)-B^∗2705. We found that cross-reactive CD8⁺ T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B^∗2705⁺ individuals. A protective CD8⁺ T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.