title: T cell responses in HIV type 1-infected adolescent minorities share similar epitope specificities with whites despite significant differences in HLA class I alleles.
abstract: African-Americans (AFAM) and Hispanics (HIS) represent only 13% and 12% of the U.S. population but 54% and 19%, respectively, of annually incident HIV-1 infections in the United States. The 88 patients in the current study were from U.S. racial or ethnic minority groups (72% African-American, 17% Hispanic), female (85%), and adolescent (mean age 20 years). Their HLA allele distributions were distinct from patterns in U.S. whites. Overall, HIV-1-specific T cell responses were observed in 91% of participants: 75% recognized peptides in Gag, 67% Pol, 57% Nef, and 41% Env. The patients recognized 87 (36%) of 244 Gag, Pol, Env, or Nef peptides tested. Similar to what has been seen in white cohorts, epitope-rich peptide clusters were identified within conserved functional domains in Gag matrix, Gag capsid, Pol reverse transcriptase, and Nef. Peptides representing variable regions from within the B subtype or with more changes from the B subtype consensus sequence were less likely to stimulate a positive T cell response. A small percentage (17%) of unique T cell responses was found in this cohort that displayed no previously known T cell epitopes. Dominant responses generally overlapped with epitope-rich regions in HIV-1 described previously for whites, although many of these peptides were likely restricted by HLA class I alleles not previously associated with these epitopes. Hence host genetic variation among different racial groups may have less impact on the utility of candidate HIV-1 vaccines than previously suspected.
authors.affiliation: Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. abansal@uab.edu
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: Steffanie
authors.initials: S
authors.lastname: Sabbaj
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Edwards
authors.forename: Doug
authors.initials: D
authors.lastname: Ritter
authors.forename: Christopher
authors.initials: C
authors.lastname: Perkins
authors.forename: James
authors.initials: J
authors.lastname: Tang
authors.forename: James J
authors.initials: JJ
authors.lastname: Szinger
authors.forename: Heidi
authors.initials: H
authors.lastname: Weiss
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D044383:Black People; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D015497:HIV-1 / Q000276:immunology*; D006630:Hispanic or Latino; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012191:Retroviridae Proteins / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D044465:White People; D001741:Black or African American
chemical_list: D019380:Anti-HIV Agents; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D012191:Retroviridae Proteins