Killer cell Immunoglobulin-like Receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition

Hdl Handle:
http://hdl.handle.net/10034/606045
Title:
Killer cell Immunoglobulin-like Receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition
Authors:
Saunders, Philippa M.; Pymm, Phillip; Pietra, Gabriella; Hughes, Victoria A.; Hitchen, Corinne; O'Connor, Geraldine M.; Loiacono, Fabrizio; Widjaja, Jacqueline M.; Price, David A.; Falco, Michela; Mingari, Maria C.; Moretta, Lorenzo; McVicar, Daniel W.; Rossjohn, Jamie; Brooks, Andrew G.; Vivian, Julian P.
Abstract:
NK 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.
Affiliation:
Department 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
Citation:
Saunders, 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
Publisher:
Rockefeller University Press
Journal:
Journal of Experimental Medicine
Publication Date:
4-Apr-2016
URI:
http://hdl.handle.net/10034/606045
DOI:
10.1084/jem.20152023
Additional Links:
http://jem.rupress.org/content/early/2016/03/29/jem.20152023.abstract
Type:
Article
Language:
en_US
Description:
This is the authors accepted manuscript.
ISSN:
0022-1007
EISSN:
1540-9538
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorSaunders, Philippa M.en
dc.contributor.authorPymm, Phillipen
dc.contributor.authorPietra, Gabriellaen
dc.contributor.authorHughes, Victoria A.en
dc.contributor.authorHitchen, Corinneen
dc.contributor.authorO'Connor, Geraldine M.en
dc.contributor.authorLoiacono, Fabrizioen
dc.contributor.authorWidjaja, Jacqueline M.en
dc.contributor.authorPrice, David A.en
dc.contributor.authorFalco, Michelaen
dc.contributor.authorMingari, Maria C.en
dc.contributor.authorMoretta, Lorenzoen
dc.contributor.authorMcVicar, Daniel W.en
dc.contributor.authorRossjohn, Jamieen
dc.contributor.authorBrooks, Andrew G.en
dc.contributor.authorVivian, Julian P.en
dc.date.accessioned2016-04-20T10:47:57Zen
dc.date.available2016-04-20T10:47:57Zen
dc.date.issued2016-04-04en
dc.identifier.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.20152023en
dc.identifier.issn0022-1007en
dc.identifier.doi10.1084/jem.20152023en
dc.identifier.urihttp://hdl.handle.net/10034/606045en
dc.descriptionThis is the authors accepted manuscript.en
dc.description.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.en
dc.language.isoen_USen
dc.publisherRockefeller University Pressen
dc.relation.urlhttp://jem.rupress.org/content/early/2016/03/29/jem.20152023.abstracten
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectNatural Killer Cellsen
dc.subjectKIRen
dc.titleKiller cell Immunoglobulin-like Receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognitionen_US
dc.typeArticleen
dc.identifier.eissn1540-9538en
dc.contributor.departmentDepartment 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, USAen
dc.identifier.journalJournal of Experimental Medicineen
dc.date.accepted2016-03-15en
or.grant.openaccessYesen
rioxxterms.funderNational Health and Medical Research Council (Australia); Worldwide cancer research organisation; The Intramural program of the National Cancer Institute; Wellcome Trusten
rioxxterms.identifier.projectExternally Funded - not through Chester Universityen
rioxxterms.versionAMen
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