Innate Partnership of HLA-B and KIR3DL1 Subtypes Against HIV-1
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.
Martin, Maureen P.; Ying Qi; Xiaojiang Gao; Eriko Yamada; Jeffrey N. Martin; Florencia Fereyra; 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. McVicar; and Mary Carrington. 2007. "Innate Partnership of HLA-B and KIR3DL1 Subtypes Against HIV-1." Nature Genetics 39, (6): 733-740. http://nsuworks.nova.edu/cnso_bio_facarticles/507