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

PM Saunders; P Pymm; G Pietra; VA Hughes; C Hitchen; GM O'Connor; F Loiacono; J Widjaja; DA Price; M Falco; MC Mingari; L Moretta; DW McVicar; J Rossjohn; AG Brooks; JP Vivian

Journal article

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

PM Saunders, P Pymm, G Pietra, VA Hughes, C Hitchen, GM O'Connor, F Loiacono, J Widjaja, DA Price, M Falco, MC Mingari, L Moretta, DW McVicar, J Rossjohn, AG Brooks, JP Vivian

Journal of Experimental Medicine | Published : 2016

DOI: 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. Althou..

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University of Melbourne Researchers

Philippa Saunders Author

Phillip Pymm Author

Jamie Rossjohn Author

Andrew Brooks Author

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Funding Acknowledgements

This work was funded by grants from the National Health and Medical Research Council (NHMRC; 1016629, 1046685, 1062267) and the Worldwide Cancer Research organization (12-1076). This work was funded in part by the National Cancer Institute (ZIA BC010747) and the National Institutes of Health Intramural AIDS Targeted Antiviral Program. L. Moretta is supported by the Associazione Italiana per la Ricerca sul Cancro (9962). D.A. Price is supported by a Wellcome Trust Senior Investigator Award (100326/Z/12/Z). J. Rossjohn is supported by an Australia Fellowship from the NHMRC (AF50). J.P. Vivian is supported by an Australian Research Council DECRA Fellowship (130101504).