Journal article
Public T cell receptors confer high-avidity CD4 responses to HIV controllers
D Benati, M Galperin, O Lambotte, S Gras, A Lim, M Mukhopadhyay, A Nouël, KA Campbell, B Lemercier, M Claireaux, S Hendou, P Lechat, P De Truchis, F Boufassa, J Rossjohn, JF Delfraissy, F Arenzana-Seisdedos, LA Chakrabarti
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2016
DOI: 10.1172/JCI83792
Abstract
The rare patients who are able to spontaneously control HIV replication in the absence of therapy show signs of a particularly efficient cellular immune response. To identify the molecular determinants that underlie this response, we characterized the T cell receptor (TCR) repertoire directed at Gag293, the most immunoprevalent CD4 epitope in the HIV-1 capsid. HIV controllers from the ANRS CODEX cohort showed a highly skewed TCR repertoire that was characterized by a predominance of TRAV24 and TRBV2 variable genes, shared CDR3 motifs, and a high frequency of public clonotypes. The most prevalent public clonotypes generated TCRs with affinities at the higher end of values reported for natural..
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Awarded by National Institutes of Health
Funding Acknowledgements
This study was carried out in the framework of the ANRS EP36 HIV Controllers Study Group, We are grateful to the patients who participated in the study. We thank the clinicians who recruited patients for this study: Huguette Berthe, David Zucman, Dominique Bornarel, Olivier Bouchaud, Patricia Honore, Philippe Genet, Juliette Gerbe, Olivier Patey, Laurent Richier, Katia Bourdic, Pierre-Marie Girard, Benedicte Lefebvre, Michele Pauchard, Jean-Michel Molina, Sylvie Parlier, Caroline Lascaux-Combe, Samuel Ferret, Valerie Garrait, and Isabelle DeLacroix-Szmania. We thank Pierre Charneau, Mirjam Heemskerk, Fabrice Lemaitre, Bernard Maillere, Christiane Moog, Olivier Schwartz, and Philippe Souque for advice and reagents; the team of the Pasteur Center for Human Immunology for help with cell sorting; and the team of the NIH Tetmmer Core facility at Emory University for reagents and advice on tetramer loading. This work was supported by ANRS, Sidaction, the Pasteur Institute, the Australian Research Council (ARC), and the National Health and Medical Research Council of Australia (NHMRC). L.A. Chakrabarti is supported by grants grants from ANRS (EP36-8) and Agence Nationale de la Recherche (ANR PD1VAX); S. Gras is supported by an ARC Future Fellowship (FF120100416), and J. Rossjohn by an NHMRC Australia Fellowship (AF50). D. Benati was the recipient of postdoctoral fellowships from ANRS, the Fondation pour la Recherche Medicale, and the Institut Sender. M. Galperin is the recipient of an ANRS doctoral fellowship, M. Mukhopadhyay is a scholar in the Pasteur - Paris University (PPU) International PhD program.