Influence of HLA-C expression level on HIV control

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. DennyXue 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)87-91
Number of pages5
JournalScience
Volume340
Issue number6128
DOIs
StatePublished - Apr 5 2013

ASJC Scopus subject areas

  • General

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    Apps, R., Qi, Y., Carlson, J. M., Chen, H., Gao, X., Thomas, R., Yuki, Y., Del Prete, G. Q., Goulder, P., Brumme, Z. L., Brumme, C. J., John, M., Mallal, S., Nelson, G., Bosch, R., Heckerman, D., Stein, J. L., Soderberg, K. A., Moody, M. A., ... Carrington, M. (2013). Influence of HLA-C expression level on HIV control. Science, 340(6128), 87-91. https://doi.org/10.1126/science.1232685