title: The size of the synaptic cleft and distinct distributions of filamentous actin, ezrin, CD43, and CD45 at activating and inhibitory human NK cell immune synapses.
abstract: In this study, we report the organization of cytoskeletal and large transmembrane proteins at the inhibitory and activating NK cell immunological or immune synapse (IS). Filamentous actin accumulates at the activating, but not the inhibitory, NK cell IS. However, surprisingly, ezrin and the associated protein CD43 are excluded from the inhibitory, but not the activating, NK cell IS. This distribution of ezrin and CD43 at the inhibitory NK cell IS is similar to that previously seen at the activating T cell IS. CD45 is also excluded from the inhibitory, but not activating, NK cell IS. In addition, electron microscopy reveals wide and narrow domains across the synaptic cleft. Target cell HLA-C, located by immunogold labeling, clusters where the synaptic cleft spans the size of HLA-C bound to the inhibitory killer Ig-like receptor. These data are consistent with assembly of the NK cell IS involving a combination of cytoskeletal-driven mechanisms and thermodynamics favoring the organization of receptor/ligand pairs according to the size of their extracellular domains.
authors.affiliation: Department of Biological Sciences, Imperial College, London, United Kingdom.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: McCann
authors.forename: Bruno
authors.initials: B
authors.lastname: Vanherberghen
authors.forename: Konstantina
authors.initials: K
authors.lastname: Eleme
authors.forename: Leo M
authors.initials: LM
authors.lastname: Carlin
authors.forename: Ray J
authors.initials: RJ
authors.lastname: Newsam
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Davis
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D015703:Antigens, CD; D002450:Cell Communication / Q000276:immunology; D002461:Cell Line, Transformed; D002999:Clone Cells; D003598:Cytoskeletal Proteins; D003602:Cytotoxicity, Immunologic; D015236:HLA-C Antigens / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000378:metabolism* / Q000648:ultrastructure; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism* / Q000648:ultrastructure; D011971:Receptors, Immunologic / Q000096:biosynthesis; D054342:Receptors, KIR2DL1; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000378:metabolism* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D000099149:Ezrin
chemical_list: D000199:Actins; D015703:Antigens, CD; D003598:Cytoskeletal Proteins; D015236:HLA-C Antigens; D017493:Leukocyte Common Antigens; D051917:Leukosialin; D010750:Phosphoproteins; D011971:Receptors, Immunologic; D054342:Receptors, KIR2DL1; D012795:Sialoglycoproteins; D000099149:Ezrin; C465014:SPN protein, human