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49 Clustering of Dominant CTL Epitopes in a Cohort of HIV+ Minority Adolescents
A. Bansal*, S. Sabbaj, B. Edwards, D. Ritter, J. Tang, B. Korber, R. Kaslow, C. Wilson, P. Goepfert, and M. Mulligan
Univ. of Alabama at Birmingham, USA
Background: Most described HIV-1 CTL epitopes were identified in Caucasian adults. To aid in the design of multi-epitope CTL vaccines, it is necessary to map new CTL epitopes in other racial/ethnic groups. Our objective was to identify dominant T-cell epitopes in a cohort of minority adolescents.
Methods: Subjects were selected from the REACH study of the Adolescent Medicine HIV/AIDS Research Network. PBMC from 60 donors (70% African-American, 18% Hispanic, and 12% Caucasian or other) were stimulated with HIV-1 clade B peptides (20-mers overlapping by 10) spanning Gag, Pol, Nef, and Env. HIV-1-specific CD8+ T-cell responses were enumerated by an IFN-gamma ELISPOT assay. Dominant epitopes were identified.
Results: Overall 88% of subjects had HIV-1-specific T-cell responses (59% Gag, 50% Nef, 47% Pol, and 25% Env). T-cell depletions indicated the responses were mediated by CD8+ T cells. A total of 233 positive responses to 84 different epitope-containing 20-mers were identified in 60 subjects (90 Gag, 70 Nef, 54 Pol, and 19 Env). Mean number of peptides recognized by subjects was 3; 25% of subjects responded to >5 peptides. Most reactive peptides (50/84, 60%) were present in clusters as follows. In Nef, the reactive peptides were clustered at aa 61(150 and aa 161(200. The N-terminal half of Gag accounted for most Gag epitopes (72%) compared with the C terminus (28%). In RT, 2 main clusters of epitopes were found (aa 251(340, 521(580). Peptides containing novel epitopes were identified in protease (aa 61(80, 121(140, and 131(150) and integrase (aa 871(890 and 901(930). In Env, clusters of epitopes were mapped in the C1 region (aa 23(60) of gp120 and the cytoplasmic domain (aa 791(856) of gp41. Conclusions: Dominant CD8+ T-cell epitopes in a cohort of minority adolescents occur in epitope-rich clusters in Gag, Pol, and Nef. These data will be useful in designing a broadly protective vaccine for HIV.
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