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 HLA–B7 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.