Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1

Maureen P. Martin, Ying Qi, Xiaojiang Gao, Eriko Yamada, Jeffrey N. Martin, Florencia Pereyra, Sara Colombo, Elizabeth E. Brown, W. Lesley Shupert, John Phair, James J. Goedert, Susan Buchbinder, Gregory D. Kirk, Amalio Telenti, Mark Connors, Stephen J. O'Brien, Bruce D. Walker, Peter Parham, Steven G. Deeks, Daniel W. McVicarMary Carrington

Research output: Contribution to journalArticle

Abstract

Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection.

Original languageEnglish (US)
Pages (from-to)733-740
Number of pages8
JournalNature genetics
Volume39
Issue number6
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Genetics

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    Martin, M. P., Qi, Y., Gao, X., Yamada, E., Martin, J. N., Pereyra, F., Colombo, S., Brown, E. E., Shupert, W. L., Phair, J., Goedert, J. J., Buchbinder, S., Kirk, G. D., Telenti, A., Connors, M., O'Brien, S. J., Walker, B. D., Parham, P., Deeks, S. G., ... Carrington, M. (2007). Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nature genetics, 39(6), 733-740. https://doi.org/10.1038/ng2035