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

Philippa M. Saunders, Phillip Pymm, Gabriella Pietra, Victoria A. Hughes, Corinne Hitchen, Geraldine M. O'Connor, Fabrizio Loiacono, Jacqueline M L Widjaja, David A. Price, Michela Falco, Maria Cristina Mingari, Lorenzo Moretta, Daniel W. McVicar, Jamie Rossjohn, Andrew G. Brooks, Julian P. Vivian

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)791-807
Number of pages17
JournalJournal of Experimental Medicine
Volume213
Issue number5
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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