The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online September 24, 2007
doi:10.1084/jem.20070784
The Journal of Experimental Medicine, Vol. 204, No. 10, 2473-2485
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Almeida et al.
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ARTICLE

 Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover

Jorge R. Almeida1, David A. Price4,5, Laura Papagno1, Zaïna Aït Arkoub2, Delphine Sauce1, Ethan Bornstein4, Tedi E. Asher4, Assia Samri1, Aurélie Schnuriger1, Ioannis Theodorou1, Dominique Costagliola3, Christine Rouzioux6, Henri Agut2, Anne-Geneviève Marcelin2, Daniel Douek4, Brigitte Autran1, and Victor Appay1

1 Cellular Immunology Laboratory, U543, Institut National de la Santé et de la Recherche Médicale (INSERM), Avenir Group, 2 Virology Laboratory, UPRES EA2387, and 3 U720, INSERM, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris6, 75013 Paris, France
4 Human Immunology Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892
5 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, England, UK
6 Virology Laboratory, Hôpital Necker-Enfants Malades, Université René Descartes-Paris5, 75015 Paris, France

CORRESPONDENCE Victor Appay: appay{at}chups.jussieu.fr

The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.

Abbreviations used: APC, allophycocyanin; CCR, CC chemokine receptor; cVL, cell-associated HIV–DNA load; MFI, median fluorescence intensity; MIP, macrophage inflammatory protein; PD-1, programmed death–1; pVL, plasma HIV–RNA load; SFU, spot-forming unit.


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