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: | 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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