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

• DOI: 10.1084/jem.20070784
• Publication Date: 2007-09-25T00:44:19Z
• Authors: Jorge R. Almeida; David A. Price; Laura Papagno; Zaïna Aït Arkoub; Delphine Sauce; Ethan Bornstein; Tedi E. Asher; Assia Samri; Aurélie Schnuriger; Ioannis Theodorou; Dominique Costagl...; Christine Rouzioux; Henri Agut; Anne-Geneviève M...; Daniel Douek; Brigitte Autran; Victor Appay
• Keywords: [SDV.IMM] Life Sciences [q-bio]/Immunology; [SDV]Life Sciences [q-bio]; Molecular Sequence Data; Gene Products, gag; HIV Infections; Articles; CD8-Positive T-Lymphocytes; Virus Replication; 3. Good health; [SDV] Life Sciences [q-bio]; 03 medical and health sciences; CD57 Antigens; 0302 clinical medicine; HIV-1; [SDV.IMM]Life Sciences [q-bio]/Immunology; Humans; Amino Acid Sequence; Lymphocyte Count; Cellular Senescence; HLA-B27 Antigen; Cell Proliferation

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.