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56 Important Contribution of p15 Gag-Specific Responses to the Total Gag-Specific CTL Responses
X. G. Yu*1,2, H. Shang2, M. M. Addo1, R. Eldridge1, M. N. Philips1, D. Strick1, C. Brander1, P. J. R. Goulder1,3, E. S. Rosenberg1, B. D. Walker1, and M. Altfeld1
1Massachusetts Gen. Hosp./Harvard Med. Sch., Boston, USA; 2First Affiliated Hosp. China Med. Univ., Shenyang, China; and 3John Radcliffe Hosp., Oxford, UK
Background: HIV-1 p15(Gag) and its protease cleavage products, NCp7 and p6, are believed to play a major role in viral infectivity and assembly during the early and late stages of retroviral life cycle. Even though HIV-1-specific CTL responses to p24(Gag) and p17(Gag) have been investigated in detail, the extent to which p15 is targeted in natural infection as well as precise CTL epitopes within this protein remains to be defined.
Methods: In this study, 57 HIV-1-infected individuals and 10 HIV-1-negative controls were screened for CD8+ and CD4+ T-cell responses against HIV-1 p15(Gag) using overlapping peptides spanning the entire p15 protein. Peptide-specific IFN-gamma production was measured by ELISPOT assay and flow-based intracellular cytokine quantification and cytotoxic activity were confirmed after isolation of peptide-specific CD8+ T-cell lines.
Results: p15-specific IFN-gamma production by T lymphocytes was found in up to 45.6%(26/57) of HIV-1-infected individuals. CD8+ T-cell responses directed against p15 were clustered within 3 immunodominant regions and contributed importantly to the total Gag-specific T-cell responses. In addition, the first 3 CTL epitopes within p15 are reported in this study, 1 of them restricted by HLA-A*0201.
Conclusions: p15 is frequently recognized by HIV-1-specific CD8+T cells in natural HIV-1 infection and may be an important target for the design of future HIV-1 vaccines.
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