title: Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition.
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.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Philippa M
authors.initials: PM
authors.lastname: Saunders
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Phillip
authors.initials: P
authors.lastname: Pymm
authors.affiliation: Department of Experimental Medicine, University of Genova, 16132 Genoa, Italy IRCCS AOU San Martino-IST (National Institute for Cancer Research), 16132 Genoa, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pietra
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Hughes
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Corinne
authors.initials: C
authors.lastname: Hitchen
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Connor
authors.affiliation: IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loiacono
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Widjaja
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Falco
authors.affiliation: Department of Experimental Medicine, University of Genova, 16132 Genoa, Italy IRCCS AOU San Martino-IST (National Institute for Cancer Research), 16132 Genoa, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
authors.affiliation: IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute-Frederick, Frederick, MD 21701.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: McVicar
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK jamie.rossjohn@monash.edu agbrooks@unimelb.edu.au julian.vivian@monash.edu.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia jamie.rossjohn@monash.edu agbrooks@unimelb.edu.au julian.vivian@monash.edu.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia jamie.rossjohn@monash.edu agbrooks@unimelb.edu.au julian.vivian@monash.edu.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Vivian
mesh_terms: D020816:Amino Acid Motifs; D002460:Cell Line; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology; D008297:Male; D011110:Polymorphism, Genetic; D054341:Receptors, KIR3DL1 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1