Victor Appay1, Maria C Iglesias. 1. INSERM UMR S 945, Infections and Immunity, Avenir Group, Hôpital Pitié-Salpêtrière, Paris, France. victor.appay@upmc.fr
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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-infectedpatients 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. SUMMARY: 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.
Authors: Maria Candela Iglesias; Jorge R Almeida; Solène Fastenackels; David J van Bockel; Masao Hashimoto; Vanessa Venturi; Emma Gostick; Alejandra Urrutia; Linda Wooldridge; Mathew Clement; Stéphanie Gras; Pascal G Wilmann; Brigitte Autran; Arnaud Moris; Jamie Rossjohn; Miles P Davenport; Masafumi Takiguchi; Christian Brander; Daniel C Douek; Anthony D Kelleher; David A Price; Victor Appay Journal: Blood Date: 2011-07-06 Impact factor: 22.113
Authors: Benoît Vingert; Daniela Benati; Olivier Lambotte; Pierre de Truchis; Laurence Slama; Patricia Jeannin; Moran Galperin; Santiago Perez-Patrigeon; Faroudy Boufassa; William W Kwok; Fabrice Lemaître; Jean-François Delfraissy; Jacques Thèze; Lisa A Chakrabarti Journal: J Virol Date: 2012-07-25 Impact factor: 5.103