title: Coordinated expression of DNAM-1 and LFA-1 in educated NK cells.
abstract: The functional capacity of NK cells is dynamically tuned by integrated signals from inhibitory and activating cell surface receptors in a process termed NK cell education. However, the understanding of the cellular and molecular mechanisms behind this functional tuning is limited. In this study, we show that the expression of the adhesion molecule and activation receptor DNAX accessory molecule 1 (DNAM-1) correlates with the quantity and quality of the inhibitory input by HLA class I-specific killer cell Ig-like receptors and CD94/NKG2A as well as with the magnitude of functional responses. Upon target cell recognition, the conformational state of LFA-1 changed in educated NK cells, associated with rapid colocalization of both active LFA-1 and DNAM-1 at the immune synapse. Thus, the coordinated expression of LFA-1 and DNAM-1 is a central component of NK cell education and provides a potential mechanism for controlling cytotoxicity by functionally mature NK cells.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden;
authors.forename: Monika
authors.initials: M
authors.lastname: Enqvist
authors.affiliation: K.G. Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway;
authors.forename: Eivind Heggernes
authors.initials: EH
authors.lastname: Ask
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Elin
authors.initials: E
authors.lastname: Forslund
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden; Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlsten
authors.affiliation: Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway; and.
authors.forename: Greger
authors.initials: G
authors.lastname: Abrahamsen
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden;
authors.forename: Vivien
authors.initials: V
authors.lastname: Béziat
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden;
authors.forename: Sandra
authors.initials: S
authors.lastname: Andersson
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden;
authors.forename: Marie
authors.initials: M
authors.lastname: Schaffer
authors.affiliation: Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway; and.
authors.forename: Anne
authors.initials: A
authors.lastname: Spurkland
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden;
authors.forename: Yenan
authors.initials: Y
authors.lastname: Bryceson
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, 106 91 Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Önfelt
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden; K.G. Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway; kalle.malmberg@ki.se.
authors.forename: Karl-Johan
authors.initials: KJ
authors.lastname: Malmberg
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers; D015870:Gene Expression; D006801:Humans; D054992:Immunological Synapses / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics* / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000378:metabolism; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D000098862:T Lineage-Specific Activation Antigen 1; D016169:Lymphocyte Function-Associated Antigen-1; D055607:Receptors, Natural Killer Cell