Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition

Saunders, Philippa M., Pymm, Phillip, Pietra, Gabriella, Hughes, Victoria A., Hitchen, Corinne, O?Connor, Geraldine M., Loiacono, Fabrizio, Widjaja, Jacqueline, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Falco, Michela, Mingari, Maria Cristina, Moretta, Lorenzo, McVicar, Daniel W., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Brooks, Andrew G. and Vivian, Julian P. 2016. Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition. Journal of Experimental Medicine 213 (5) , pp. 791-807. 10.1084/jem.20152023

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Abstract

Natural killer (NK) cells play a key role in immunity, but how HLA class I (HLA-I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism impacts disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognizing the widest array of HLA-I ligands. These differences were further reflected in functional studies using NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005, and *015 polymorphisms are remote from the KIR3DL1–HLA-I interface, the structures of these three KIR3DL1–HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Rockefeller University Press
ISSN:	0022-1007
Date of First Compliant Deposit:	15 February 2017
Date of Acceptance:	15 March 2016
Last Modified:	19 Nov 2023 15:55
URI:	https://orca.cardiff.ac.uk/id/eprint/98324

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