title: TCR clonotypes: molecular determinants of T-cell efficacy against HIV.
abstract: Because of the enormous complexity and breadth of the overall HIV-specific CD8(+) T-cell response, invaluable information regarding important aspects of T-cell efficacy against HIV can be sourced from studies performed on individual clonotypes. Data gathered from ex vivo and in vitro analyses of T-cell responses and viral evolution bring us one step closer towards deciphering the correlates of protection against HIV. HIV-responsive CD8(+) T-cell populations are characterized by specific clonotypic immunodominance patterns and public TCRs. The TCR endows T-cells with two key features, important for the effective control of HIV: avidity and crossreactivity. While TCR avidity is a major determinant of CD8(+) T-cell functional efficacy against the virus, crossreactivity towards wildtype and mutant viral epitopes is crucial for adaptation to HIV evolution. The properties of CD4(+) T-cell responses in HIV controllers appear also to be shaped by high avidity public TCR clonotypes. The molecular nature of the TCR, together with the clonotypic composition of the HIV-specific T-cell response, emerge as major determinants of anti-viral efficacy.
authors.affiliation: Faculty of Medical and Veterinary Sciences, Biomedical Sciences Building, University of Bristol, Bristol BS81TD, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Lissina
authors.affiliation: Pasteur Institute, Viral Pathogenesis Unit, Paris, France; INSERM U1108, Paris, France.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Chakrabarti
authors.affiliation: Center for AIDS Research and International Research Center of Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), F-75013 Paris, France; INSERM U1135, CIMI-Paris, F-75013 Paris, France. Electronic address: victor.appay@upmc.fr.
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
mesh_terms: D000818:Animals; D003429:Cross Reactions / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology
chemical_list: D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell