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55 New Cytotoxic T-Cell Epitopes and MHC Restrictions in HIV-Infected African-American Adolescents
S. Sabbaj*, A. Bansal, D. Ritter, C. Perkins, B. Edwards, J. Tang, B. Korber, C. Wilson, R. Kaslow, P. Goepfert, and M. Mulligan
Univ. of Alabama at Birmingham, USA
Background: Class I MHC molecules restrict CD8+ CTL responses. Versatile application of CTL vaccines in different racial or ethnic groups will require inclusion of immunodominant T-cell epitopes restricted by a variety of class I MHC molecules. To facilitate development of a widely applicable HIV vaccine, this study aims to identify new CD8+ T-cell epitopes in HIV-infected African-Americans.
Methods: Subjects were selected from the REACH study of the Adolescent Medicine HIV/AIDS Research Network. From this cohort, PBMCs from 15 volunteers were used to derive T-cell lines using nonspecific stimulation. Lines with HIV-specific lytic activity were identified in a 51Cr-release assay employing BLCL targets pulsed with peptide pools spanning HIV-1 clade B Gag, Pol, Env, or Nef. Positive lines were expanded, and further epitope mapping was performed using an interferon-gamma ELISPOT assay. HLA-mismatched BLCL targets in the 51Cr-release assay were used to define MHC-restriction of peptides.
Results: From the 15 volunteers we obtained 52 HIV-specific cell lines, of which 28 had unique specificities. Seventeen lines were class I MHC-restricted and 11 were mapped to their optimum peptide (9(11 aa). Nine of those 11 epitopes were also identified separately by PBMC mapping. We detected 7 new HIV epitopes and/or MHC restrictions. Two epitopes have not been reported before: a Pol epitope (KIQNFRVYY, aa# 934(942) restricted by A*3002 (an HLA allele present in 15% of African-Americans) and a Gag epitope (GELDRWEKIRL, aa# 11(21) restricted by B*4002. Each of the other 5 epitopes have newly recognized restricting MHC proteins, 1 of which (B*1503) occurs in about 5% of African-Americans and 10% of East Africans. Four of the T-cell lines targeted previously described HIV peptide/MHC protein complexes.
Conclusions: Identification of new MHC-restricted CTL epitopes in young African-Americans is highly relevant to the development of CTL vaccines for global use.
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