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Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1
Martin, Maureen P. Naranbhai, Vivek Shea, Patrick R. Qi, Ying Ramsuran, Veron Vince, Nicolas Gao, Xiaojiang Thomas, Rasmi Brumme, Zabrina L. Carlson, Jonathan M.
Martin, Maureen P.
Naranbhai, Vivek
Shea, Patrick R.
Qi, Ying
Ramsuran, Veron
Vince, Nicolas
Gao, Xiaojiang
Thomas, Rasmi
Brumme, Zabrina L.
Carlson, Jonathan M.
Author
Martin, Maureen P.
Naranbhai, Vivek
Shea, Patrick R.
Qi, Ying
Ramsuran, Veron
Vince, Nicolas
Gao, Xiaojiang
Thomas, Rasmi
Brumme, Zabrina L.
Carlson, Jonathan M.
Wolinsky, Steven M.
Goedert, James J.
Walker, Bruce D.
Segal, Florencia P.
Deeks, Steven G.
Haas, David W.
Migueles, Stephen A.
Connors, Mark
Michael, Nelson
Fellay, Jacques
Gostick, Emma
Llewellyn-Lacey, Sian
Price, David A.
Lafont, Bernard A.
Pymm, Phillip
Saunders, Philippa M.
Widjaja, Jacqueline
Wong, Shu Cheng
Vivian, Julian P.
Rossjohn, Jamie
Brooks, Andrew G.
Carrington, Mary
Naranbhai, Vivek
Shea, Patrick R.
Qi, Ying
Ramsuran, Veron
Vince, Nicolas
Gao, Xiaojiang
Thomas, Rasmi
Brumme, Zabrina L.
Carlson, Jonathan M.
Wolinsky, Steven M.
Goedert, James J.
Walker, Bruce D.
Segal, Florencia P.
Deeks, Steven G.
Haas, David W.
Migueles, Stephen A.
Connors, Mark
Michael, Nelson
Fellay, Jacques
Gostick, Emma
Llewellyn-Lacey, Sian
Price, David A.
Lafont, Bernard A.
Pymm, Phillip
Saunders, Philippa M.
Widjaja, Jacqueline
Wong, Shu Cheng
Vivian, Julian P.
Rossjohn, Jamie
Brooks, Andrew G.
Carrington, Mary
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.
Keywords
Date
2018
Type
Journal article
Journal
Journal of Clinical Investigation
Book
Volume
128
Issue
5
Page Range
1903-1912
Article Number
ACU Department
Marketing and Communications
Research Office
Research Office
Collections
Relation URI
DOI
Source URL
Event URL
Open Access Status
License
All rights reserved
File Access
Controlled