T cell responses in HIV type 1-infected adolescent minorities share similar epitope specificities with whites despite significant differences in HLA class I alleles

AIDS Res Hum Retroviruses. 2003 Nov;19(11):1017-26. doi: 10.1089/088922203322588378.

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.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Amino Acid Sequence
  • Anti-HIV Agents / therapeutic use
  • Black People
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • HIV Infections / ethnology*
  • HIV Infections / genetics*
  • HIV-1 / immunology*
  • Hispanic or Latino
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Testing
  • Humans
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / immunology
  • Retroviridae Proteins / chemistry
  • Retroviridae Proteins / immunology
  • T-Lymphocytes / immunology*
  • White People

Substances

  • Anti-HIV Agents
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Peptides
  • Retroviridae Proteins