%0 Journal Article
%T Killer cell immunoglobulin¨Clike receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1
%A Andrew G. Brooks
%A Bernard A. Lafont
%A Bruce D. Walker
%A David A. Price
%A David W. Haas
%A Emma Gostick
%A Florencia P. Segal
%A Jacqueline Widjaja
%A Jacques Fellay
%A James J. Goedert
%A Jamie Rossjohn
%A Jonathan M. Carlson
%A Julian P. Vivian
%A Mark Connors
%A Mary Carrington
%A Maureen P. Martin
%A Nelson Michael
%A Nicolas Vince
%A Patrick R. Shea
%A Philippa M. Saunders
%A Phillip Pymm
%A Rasmi Thomas
%A Shu Cheng Wong
%A Sian Llewellyn-Lacey
%A Stephen A. Migueles
%A Steven G. Deeks
%A Steven M. Wolinsky
%A Veron Ramsuran
%A Vivek Naranbhai
%A Xiaojiang Gao
%A Ying Qi
%A Zabrina L. Brumme
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI98463
%X 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¨Cinfected 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
%U https://www.jci.org/articles/view/98463