title: Putative immunodominant human immunodeficiency virus-specific CD8(+) T-cell responses cannot be predicted by major histocompatibility complex class I haplotype.
abstract: Recent studies of human immunodeficiency virus (HIV)-specific CD8(+) T cells have focused on responses to single, usually HLA-A2-restricted epitopes as surrogate measures of the overall response to HIV. However, the assumption that a response to one epitope is representative of the total response is unconfirmed. Here we assess epitope immunodominance and HIV-specific CD8(+) T-cell response complexity using cytokine flow cytometry to examine CD8(+) T-cell responses in 11 HLA-A2(+) HIV(+) individuals. Initial studies demonstrated that only 4 of 11 patients recognized the putative immunodominant HLA-A2-restricted p17 epitope SLYNTVATL, suggesting that the remaining subjects might lack significant HIV-specific CD8(+) T-cell responses. However, five of six SLYNTVATL nonresponders recognized other HIV epitopes, and two of four SLYNTVATL responders had greater responses to HIV peptides restricted by other class I alleles. In several individuals, no HLA-A2-restricted epitopes were recognized, but CD8(+) T-cell responses were detected to epitopes restricted by other HLA class I alleles. These data indicate that an individual's overall CD8(+) T-cell response to HIV is not adequately represented by the response to a single epitope and that individual major histocompatibility complex class I alleles do not predict an immunodominant response restricted by that allele. Accurate quantification of total HIV-specific CD8(+) T-cell responses will require assessment of the response to all possible epitopes.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Betts
authors.forename: J P
authors.initials: JP
authors.lastname: Casazza
authors.forename: B A
authors.initials: BA
authors.lastname: Patterson
authors.forename: S
authors.initials: S
authors.lastname: Waldrop
authors.forename: W
authors.initials: W
authors.lastname: Trigona
authors.forename: T M
authors.initials: TM
authors.lastname: Fu
authors.forename: F
authors.initials: F
authors.lastname: Kern
authors.forename: L J
authors.initials: LJ
authors.lastname: Picker
authors.forename: R A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans
chemical_list: D015395:Histocompatibility Antigens Class I