Functional analysis of T cell responses in HIV-infected individuals has indicated that virus-specific CD8+ T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progressors. To define the role of individual TCR clonotypes in differential antiviral CD8+ T cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8+ T cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK). Effective and ineffective CD8+ T cell clones segregated based on responses to HIV-1-infected and peptide-loaded target cells. Following cognate peptide stimulation, effective HIV-specific clones displayed significantly more rapid TCR signal propagation, more efficient initial lytic granule release and more sustained non-lytic cytokine and chemokine secretion compared to ineffective clones. To evaluate TCR clonotype contribution to CD8+ T cell function, we cloned the TCR α and β chain genes from one effective and two ineffective CD8+ T cell clones from an elite controller into TCR-expressing lentivectors. We show that Jurkat/MA cells and primary CD8+ T cells transduced with lentivirus expressing TCR from one of the ineffective clones exhibited comparable activation by cognate peptide as the effective clonotype, and comparable inhibition of in vitro HIV-1 infection, respectively. Taken together, these data suggest that the potent antiviral capacity of some HIV-specific CD8+ T cells is a consequence of factors in addition to TCR sequence that modulate functionality and contribute to the increased antiviral capacity of HIV-specific CD8+ T cells in elite controllers to inhibit HIV infection.