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

DOI PDF 5 Citations
  • Philippa M. Saunders
    Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia 1
  • Phillip Pymm
    Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia 2
  • Gabriella Pietra
    Department of Experimental Medicine, University of Genova, 16132 Genoa, Italy 5
  • Victoria A. Hughes
    Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia 2
  • Corinne Hitchen
    Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia 2
  • Geraldine M. O’Connor
    Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia 1
  • Fabrizio Loiacono
    IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy 7
  • Jacqueline Widjaja
    Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia 1
  • David A. Price
    Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK 8
  • Michela Falco
    IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy 7
  • Maria Cristina Mingari
    Department of Experimental Medicine, University of Genova, 16132 Genoa, Italy 5
  • Lorenzo Moretta
    IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy 10
  • Daniel W. McVicar
    Cancer and Inflammation Program, National Cancer Institute–Frederick, Frederick, MD 21701 11
  • Jamie Rossjohn
    Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia 2
  • Andrew G. Brooks
    Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia 1
  • Julian P. Vivian
    Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia 2

Description

<jats:p>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.</jats:p>

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