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Carrington, Mary; Martin, Maureen P; Qi, Ying; Gao, Xiaojiang; Yamada, Eriko; Martin, Jeffrey N; Pereyra, Florencia; Colombo, Sara; Brown, Elizabeth E; Shupert, W Lesley; Phair, John; Goedert, James J; Buchbinder, Susan; Kirk, Gregory D; Telenti, Amalio; Connors, Mark; O'Brien, Stephen J; Walker, Bruce D; Parham, Peter; Deeks, Steven G; McVicar, Daniel W
Nature genetics, 06/2007, Letnik: 39, Številka: 6Journal Article
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.
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