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Influence of HLA-C expression level on HIV control.

Science (New York, N.Y.) (2013-04-06)
Richard Apps, Ying Qi, Jonathan M Carlson, Haoyan Chen, Xiaojiang Gao, Rasmi Thomas, Yuko Yuki, Greg Q Del Prete, Philip Goulder, Zabrina L Brumme, Chanson J Brumme, Mina John, Simon Mallal, George Nelson, Ronald Bosch, David Heckerman, Judy L Stein, Kelly A Soderberg, M Anthony Moody, Thomas N Denny, Xue Zeng, Jingyuan Fang, Ashley Moffett, Jeffrey D Lifson, James J Goedert, Susan Buchbinder, Gregory D Kirk, Jacques Fellay, Paul McLaren, Steven G Deeks, Florencia Pereyra, Bruce Walker, Nelson L Michael, Amy Weintrob, Steven Wolinsky, Wilson Liao, Mary Carrington
PMID23559252
ABSTRACT

A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.