title: HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor.
abstract: HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.
authors.affiliation: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS UK.
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Guillaume
authors.initials: G
authors.lastname: Stewart-Jones
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Xu
authors.forename: Laura
authors.initials: L
authors.lastname: Papagno
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.forename: Michael
authors.initials: M
authors.lastname: Weekes
authors.forename: Chris
authors.initials: C
authors.lastname: Conlon
authors.forename: Celsa
authors.initials: C
authors.lastname: Spina
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Gavin
authors.initials: G
authors.lastname: Screaton
authors.forename: Anton
authors.initials: A
authors.lastname: van der Merwe
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: E Yvonne
authors.initials: EY
authors.lastname: Jones
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
mesh_terms: D017209:Apoptosis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015693:Gene Products, nef / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D015795:HLA-B8 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000276:immunology; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D018984:Epitopes, T-Lymphocyte; D015693:Gene Products, nef; D015795:HLA-B8 Antigen; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054311:nef Gene Products, Human Immunodeficiency Virus