HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C

Rasmi Thomas, Richard Apps, Ying Qi, Xiaojiang Gao, Victoria Male, Colm O'Huigin, Geraldine O'Connor, Dongliang Ge, Jacques Fellay, Jeffrey N. Martin, Joseph Margolick, James J. Goedert, Susan Buchbinder, Gregory D. Kirk, Maureen P. Martin, Amalio Telenti, Steven G. Deeks, Bruce D. Walker, David Goldstein, Daniel W. McVicarAshley Moffett, Mary Carrington

Research output: Contribution to journalArticlepeer-review

218 Scopus citations


A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. We show that the-35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high-expressing HLA-C alleles progress more slowly to AIDS and control viremia significantly better than individuals with low HLA-C expressing alleles. These data strongly implicate high HLA-C expression levels in more effective control of HIV-1, potentially through better antigen presentation to cytotoxic T lymphocytes or recognition and killing of infected cells by natural killer cells.

Original languageEnglish (US)
Pages (from-to)1290-1294
Number of pages5
JournalNature genetics
Issue number12
StatePublished - Dec 2009

ASJC Scopus subject areas

  • Genetics


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