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.

Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa

“…Structural similarities in MHC-binding clefts have given rise to HLA supertype groupings (50,51), although our data show that degenerate epitope binding does not adhere to known supertypes. These data extend and confirm recent data, inferring that similar epitope specificities are observed between different populations expressing divergent HLA class I alleles (52).…”

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

“…These data are consistent with previous studies indicating that the vast majority of these types of responses are due to CD8 ϩ T cells (7,8,24).…”

HIV-Specific CD8+T Cells from Elite Controllers Are Primed for Survival

“…Given the important role of CD8 T cell responses in viral control seen in nonhuman primate and human data (1,2) and the fact that HLA class I alleles are associated with differences in disease progression (3-7), many current efforts are focused on defining an optimal CD8 T cell immune response to guide effective vaccine design. Unfortunately, studies have failed to consistently demonstrate clear associations of the breadth or magnitude of the cytotoxic T lymphocyte (CTL) response with the plasma viral load (pVL) (8)(9)(10)(11). However, polyfunctional T cell responses, including the capacity to secrete cytokines, degranulate, and proliferate in response to antigen, correlate with clinical markers of disease progression (12)(13)(14)(15)(16).…”