Antigen sensitivity and T-cell receptor avidity as critical determinants of HIV control

Induction of highly effective T cells capable of performing elite control of HIV replication represents a major goal of vaccinology. Here, we review the recent evidence supporting the central role of antigen sensitivity and T-cell receptor (TCR) avidity in determining anti-HIV T-cell efficacy. We discuss why the modulation of these factors represents an interesting approach for the rational design of HIV vaccines.

The qualitative attributes of T-cell efficacy against HIV are closely related to the sensitivity of the cells for their cognate antigen, which appears essential to control viral replication in HIV-infected patients and is in turn strongly influenced by TCR avidity. High antigen sensitivity and TCR avidity present also potential caveats, notably T-cell clonal exhaustion and rapid emergence of escape variants.

The central role of antigen sensitivity and TCR avidity in determining the quality of T-cell responses against HIV represents a new development in our understanding of the immune control of HIV, and the quest for an effective vaccine. Strategies to improve T-cell efficacy in vaccination approaches may rely on selecting T cells with high antigen sensitivity during priming.