title: Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes.
abstract: The relative contributions of HLA alleles and T-cell receptors (TCRs) to the prevention of mutational viral escape are unclear. Here, we examined human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T-cell responses restricted by two closely related HLA class I alleles, B*5701 and B*5703, that differ by two amino acids but are both associated with a dominant response to the same HIV-1 Gag epitope KF11 (KAFSPEVIPMF). When this epitope is presented by HLA-B*5701, it induces a TCR repertoire that is highly conserved among individuals, cross-recognizes viral epitope variants, and is rarely associated with mutational escape. In contrast, KF11 presented by HLA-B*5703 induces an entirely different, more heterogeneous TCR beta-chain repertoire that fails to recognize specific KF11 escape variants which frequently arise in clade C-infected HLA-B*5703(+) individuals. These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Room 5212, Charlestown, MA 02129, USA.
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Senica
authors.initials: S
authors.lastname: Chetty
authors.forename: Katie L
authors.initials: KL
authors.lastname: Williams
authors.forename: Stanley K
authors.initials: SK
authors.lastname: Mui
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Tang
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Montiago X
authors.initials: MX
authors.lastname: Labute
authors.forename: Katja
authors.initials: K
authors.lastname: Pfafferott
authors.forename: Alisdair
authors.initials: A
authors.lastname: Leslie
authors.forename: Hayley
authors.initials: H
authors.lastname: Crawford
authors.forename: Rachel
authors.initials: R
authors.lastname: Allgaier
authors.forename: William
authors.initials: W
authors.lastname: Hildebrand
authors.forename: Richard
authors.initials: R
authors.lastname: Kaslow
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Madhu
authors.initials: M
authors.lastname: Vajpayee
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013045:Species Specificity
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell