Killer cell Immunoglobulin-like Receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition
AuthorsSaunders, Philippa M.
Hughes, Victoria A.
O'Connor, Geraldine M.
Widjaja, Jacqueline M.
Price, David A.
Mingari, Maria C.
McVicar, Daniel W.
Brooks, Andrew G.
Vivian, Julian P.
AffiliationDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia; Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; Department of Experimental Medicine, University of Genova, Genoa, 16132 Italy; IRCCS AOU San Martino-IST (National Institute for Cancer Research), Genoa, 16132 Italy; IRCCS Istituto Giannina Gaslini, Genoa, Italy; Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; IRCCS Ospedale Pediatrico Bambino Gesù, Roma ITALY; Cancer and Inflammation Program, National Cancer Institute-Frederick, Frederick, MD 21702, USA
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AbstractNK cells play a key role in immunity, but how HLA-I and KIR3DL1 polymorphism impacts on 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 recognising the widest array of HLA-I ligands. These differences were further reflected in unctional studies utilising 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.
CitationSaunders, P. M., Pymm, P., Pietra, G., Hughes, V. A., Hitchen, C., O'Connor, G. M., Loiacono, F., Widjaja, J., Price, D. A., Falco, M., Mingari, M. C., Moretta, L., McVicar, D. W., Rossjohn, J., Brooks, A. G., & Vivian, J. P. (2016). Killer cell Immunoglobulin-like Receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition. Journal of Experimental Medicine. http://dx.doi.org/10.1084/jem.20152023
PublisherRockefeller University Press
JournalJournal of Experimental Medicine
DescriptionThis is the authors accepted manuscript.
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