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

• Published in: The Journal of experimental medicine Vol. 204; no. 10; pp. 2473 - 2485
• Main Authors: Almeida, Jorge R., Price, David A., Papagno, Laura, Arkoub, Zaïna Aït, Sauce, Delphine, Bornstein, Ethan, Asher, Tedi E., Samri, Assia, Schnuriger, Aurélie, Theodorou, Ioannis, Costagliola, Dominique, Rouzioux, Christine, Agut, Henri, Marcelin, Anne-Geneviève, Douek, Daniel, Autran, Brigitte, Appay, Victor
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01.10.2007; The Rockefeller University Press
• Subjects: Amino Acid Sequence; CD57 Antigens - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cell Proliferation; Cellular Senescence; Gene Products, gag - immunology; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - pathology; HIV-1 - physiology; HLA-B27 Antigen - chemistry; HLA-B27 Antigen - immunology; Humans; Immunology; Life Sciences; Lymphocyte Count; Molecular Sequence Data; Virus Replication
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20070784

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.