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HLA B*5701 Is Highly Associated with Restriction of Virus Replication in a Subgroup of HIV-Infected Long Term Nonprogressors
Stephen A. Migueles, M. Shirin Sabbaghian, W. Lesley Shupert, Maria P. Bettinotti, Francesco M. Marincola, Lisa Martino, Clair W. Hallahan, Sara M. Selig, David Schwartz, John Sullivan and Mark Connors
Proceedings of the National Academy of Sciences of the United States of America
Vol. 97, No. 6 (Mar. 14, 2000), pp. 2709-2714
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/122228
Page Count: 6
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A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4+ T cell counts and <50 copies/ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0.001]. Antigen-specific CD8+ T cells were enumerated by flow cytometric detection of intracellular IFN-γ in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8+ T cell responses were observed between B*57+ LTNP and five B*57+ progressors (P = 0.4). Although similar frequencies of peptide specific CD8+ T cells were also found, the gag-specific CD8+ T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57+ LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.
Proceedings of the National Academy of Sciences of the United States of America © 2000 National Academy of Sciences