| Literature DB >> 29461980 |
Maureen P Martin1, Vivek Naranbhai2,3, Patrick R Shea4, Ying Qi1, Veron Ramsuran1,3,5, Nicolas Vince1,6,7, Xiaojiang Gao1, Rasmi Thomas8,9, Zabrina L Brumme10,11, Jonathan M Carlson12, Steven M Wolinsky13, James J Goedert14, Bruce D Walker2, Florencia P Segal15, Steven G Deeks16, David W Haas17, Stephen A Migueles18, Mark Connors18, Nelson Michael8,9, Jacques Fellay19, Emma Gostick20,21, Sian Llewellyn-Lacey20,21, David A Price20,22, Bernard A Lafont23, Phillip Pymm24, Philippa M Saunders25, Jacqueline Widjaja25, Shu Cheng Wong25, Julian P Vivian24, Jamie Rossjohn20,21,24, Andrew G Brooks25, Mary Carrington1,2.
Abstract
HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in the level of HIV control among B*57+ individuals. Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. The association was replicated in an independent cohort and across multiple outcomes. The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03. Positions 2, 47, and 54 tracked one another nearly perfectly, and 2 KIR3DL1 allotypes differing only at these 3 positions showed significant differences in binding B*57:01 tetramers, whereas the protective allotype showed lower binding. Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. These data highlight the exquisite specificity of KIR-HLA interactions in human health and disease.Entities:
Keywords: AIDS/HIV; Innate immunity; MHC class 1; NK cells
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Year: 2018 PMID： 29461980 PMCID： PMC5919796 DOI： 10.1172/JCI98463
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808