HIV-1 Specific T cell Responses Restricted by HLA-B81, -B42 and -B7 in African Zulu/Xhosa Population.

PN. Mngqundaniso1, P. Kiepiela1, D. Ramduth1, P. Chetty1, N. Ntumba1, N. Nene1, S. Gapoo1, C. Henry1, J. Harlow1, I. Honeyborne1, M. Addo2, M. Altfeld2, B. D. Walker2, H. M. Coovadia1, P. J. R. Goulder3. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of Natal1; Partners AIDS Research Centre and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School2; Nuffield Department of Medicine, Oxford University3 (UK).

Background: Cytotoxic T Lymphocytes (CTLs) have been shown to play a major role in the control of viraemia in HIV infected individuals. CTL response to HIV epitopes depends on the HLA type of the individual. This study concentrated on HLA-B7, -B42 and B81 which are some of the HLA types prevalent in this population. Material and Methods: ELISPOT assay was used for epitope screening which was then confirmed by Intracellular Cytokine Staining (ICS). HLA-B42 tetramer bound to TPQDLNTML (TL9) was used for the HLA B42 positive individuals. CD4/CD8 counts and viral load were done on all individuals. Results: There was no significance in viral load and CD4 counts between individuals expressing HLA-B7, -B42 and B81. 89% of the HLA-B81, 77% of HLA-B42 and 72% of HLA B7 individuals responded to the p24 Gag TL9 epitope. Taking the magnitude of ELISPOT assay for TL9 response, HLA- B42 was the highest with a median of 510 SFC/Mill PBMC, HLA- B81 following with a median of 440 SFC/Mill PBMC and HLAB7 had the weakest response to TL9 with a median of 105 SFC/Mill PBMC. Intracellular Cytokine Staining of TL9 specific CD8 + T cell responses was 0.83% for HLA-B42, 0.61% for HLA-B81 and 0.51% for HLA-B7 respectively. Conclusion: The majority of individuals expressing HLA-B7, -B42 and B81 have T cell responses to the p24 Gag epitope TL9. HLA-B42 and B81 individuals have stronger responses than individuals expressing HLA-B7. There was a trend towards lower viral load in the HLA-B81 individuals. These HLA-B81 individuals had significantly high CD4 T cell counts. There are several epitopes that are cross-presented by HLA-B7, -B42 and B81.