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

Journal: Nature Genetics. 2007 May 13; E-publication ahead of print.

Authors and affililation: Martin MP, Qi Y, Gao X, Yamada E, Martin JN, Pereyra F, Colombo S, Brown EE, Shupert WL, Phair J, Goedert JJ, Buchbinder S, Kirk GD, Telenti A, Connors M, O’brien SJ, Walker BD, Parham P, Deeks SG, McVicar DW, Carrington M. Laboratory of Genomic Diversity, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, Maryland, USA.

PMID: 17496894

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. [Allotypes are different DNA codings that may occupy a given position on a chromosome.]

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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