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

Appay, Victor; Iglesias, Maria C

Current Opinion in HIV and AIDS: May 2011 - Volume 6 - Issue 3 - p 157–162
doi: 10.1097/COH.0b013e3283453dfd
Elite controllers: Edited by Steven G. Deeks, Alexandre Harari and Joel Blankson

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.

INSERM UMR S 945, Infections and Immunity, Avenir Group, Hôpital Pitié-Salpêtrière, Paris, France

Correspondence to Victor Appay, INSERM UMR S 945, Infections and Immunity, Avenir Group, Hôpital Pitié-Salpêtrière, Paris, France Tel: +33 1 40 77 81 83; fax: +33 1 40 77 97 34; e-mail: victor.appay@upmc.fr

© 2011 Lippincott Williams & Wilkins, Inc.