KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progressio

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Nature Genetics
Published online: 13 May 2007 | doi:10.1038/ng2035


Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1
Maureen P Martin1, Ying Qi1, Xiaojiang Gao1, Eriko Yamada2, Jeffrey N Martin3, Florencia Pereyra4, Sara Colombo5, Elizabeth E Brown6, W Lesley Shupert7, John Phair8, James J Goedert6, Susan Buchbinder9, Gregory D Kirk10, Amalio Telenti5, Mark Connors11, Stephen J O'Brien12, Bruce D Walker4, Peter Parham13, Steven G Deeks14, Daniel W McVicar2 & Mary Carrington1


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AbstractAllotypes 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.