title: Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover.
abstract: 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.
authors: Cellular Immunology Laboratory, U543, Institut National de la Santé et de la Recherche Médicale, Avenir Group, 75013 Paris, France.
authors: Jorge R
authors: JR
authors: Almeida
authors: David A
authors: DA
authors: Price
authors: Laura
authors: L
authors: Papagno
authors: Zaïna Aït
authors: ZA
authors: Arkoub
authors: Delphine
authors: D
authors: Sauce
authors: Ethan
authors: E
authors: Bornstein
authors: Tedi E
authors: TE
authors: Asher
authors: Assia
authors: A
authors: Samri
authors: Aurélie
authors: A
authors: Schnuriger
authors: Ioannis
authors: I
authors: Theodorou
authors: Dominique
authors: D
authors: Costagliola
authors: Christine
authors: C
authors: Rouzioux
authors: Henri
authors: H
authors: Agut
authors: Anne-Geneviève
authors: AG
authors: Marcelin
authors: Daniel
authors: D
authors: Douek
authors: Brigitte
authors: B
authors: Autran
authors: Victor
authors: V
authors: Appay
mesh_terms: D000595:Amino Acid Sequence; D018959:CD57 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D016922:Cellular Senescence; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000502:physiology*; D015796:HLA-B27 Antigen / Q000737:chemistry / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D014779:Virus Replication
chemical_list: D018959:CD57 Antigens; D015683:Gene Products, gag; D015796:HLA-B27 Antigen