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

Anju Bansal, Steffanie Sabbaj, Bradley H Edwards, Doug Ritter, Christopher Perkins, James Tang, James J Szinger, Heidi Weiss, Paul A Goepfert, Bette Korber, Craig M Wilson, Richard A Kaslow, Mark J Mulligan

Journal: AIDS research and human retroviruses 2004;19(11):1017-26

PMID: 14678609

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.

Address: Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. [email protected]

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