TCR clonotypes: molecular determinants of T-cell efficacy against HIV

•HIV-specific CD8+ T-cells show TCR immunodominance patterns and public clonotypes.•TCR avidity is a major determinant of CD8+ T-cell functional efficacy against HIV.•Crossreactive clonotypes are key to adapt to HIV evolution and control the virus.•High affinity public clonotypes shape CD4+ T-cell responses in HIV controllers.

Because of the enormous complexity and breadth of the overall HIV-specific CD8+ T-cell response, invaluable information regarding important aspects of T-cell efficacy against HIV can be sourced from studies performed on individual clonotypes. Data gathered from ex vivo and in vitro analyses of T-cell responses and viral evolution bring us one step closer towards deciphering the correlates of protection against HIV. HIV-responsive CD8+ T-cell populations are characterized by specific clonotypic immunodominance patterns and public TCRs. The TCR endows T-cells with two key features, important for the effective control of HIV: avidity and crossreactivity. While TCR avidity is a major determinant of CD8+ T-cell functional efficacy against the virus, crossreactivity towards wildtype and mutant viral epitopes is crucial for adaptation to HIV evolution. The properties of CD4+ T-cell responses in HIV controllers appear also to be shaped by high avidity public TCR clonotypes. The molecular nature of the TCR, together with the clonotypic composition of the HIV-specific T-cell response, emerge as major determinants of anti-viral efficacy.