title: Cutting edge: NK cell licensing modulates adhesion to target cells.
abstract: Binding of NK cell inhibitory receptors to MHC class I (MHC-I) confers increased responsiveness to NK cells by a process known as NK cell licensing/education. Reduced MHC-I expression or a lack of inhibitory receptors for MHC-I results in diminished NK cell responsiveness. In this study, we evaluated the effect of human and mouse NK cell licensing on early stages of natural cytotoxicity. Unlicensed NK cells did not form as many stable conjugates with target cells. The reduction of NK cell conjugation to target cells was not attributed to altered β2 integrin LFA-1 properties but was instead due to reduced inside-out signaling to LFA-1 by activating receptors. For those unlicensed NK cells that did form conjugates, LFA-1-dependent granule polarization was similar to that in licensed NK cells. Thus, licensing controls signals as proximal as inside-out signaling by activating receptors but not integrin outside-in signaling for granule polarization.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: L Michael
authors.initials: LM
authors.lastname: Thomas
authors.forename: Mary E
authors.initials: ME
authors.lastname: Peterson
authors.forename: Eric O
authors.initials: EO
authors.lastname: Long
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction
chemical_list: D018821:CD18 Antigens; D015395:Histocompatibility Antigens Class I; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1
references.citation: Blood. 2009 Sep 24;114(13):2657-66
references.pmid: 19628705
references.citation: Nat Rev Immunol. 2008 Sep;8(9):713-25
references.pmid: 19172692
references.citation: J Exp Med. 2010 Sep 27;207(10):2073-9
references.pmid: 20819924
references.citation: Immunol Rev. 2006 Dec;214:56-72
references.pmid: 17100876
references.citation: Blood. 2008 Sep 15;112(6):2369-80
references.pmid: 18583565
references.citation: Nature. 2005 Aug 4;436(7051):709-13
references.pmid: 16079848
references.citation: Blood. 2007 Jul 15;110(2):578-86
references.pmid: 17392508
references.citation: Blood. 2009 Mar 12;113(11):2434-41
references.pmid: 18974374
references.citation: Trends Immunol. 2011 Aug;32(8):364-72
references.pmid: 21752715
references.citation: J Immunol. 2011 Mar 1;186(5):2998-3005
references.pmid: 21270398
references.citation: Nature. 1991 Jan 24;349(6307):329-31
references.pmid: 1987491
references.citation: J Immunol. 2009 Apr 15;182(8):4572-80
references.pmid: 19342631
references.citation: Immunity. 2006 Aug;25(2):331-42
references.pmid: 16901727
references.citation: Nat Rev Immunol. 2010 Oct;10(10):724-34
references.pmid: 20818413
references.citation: J Immunol. 1985 Aug;135(2):1020-5
references.pmid: 3924996
references.citation: J Immunol. 2004 Sep 15;173(6):3653-9
references.pmid: 15356110
references.citation: Annu Rev Immunol. 2007;25:619-47
references.pmid: 17201681
references.citation: Annu Rev Immunol. 2013;31:227-58
references.pmid: 23516982
references.citation: J Exp Med. 2005 Oct 3;202(7):1001-12
references.pmid: 16203869
references.citation: J Exp Med. 2010 Sep 27;207(10):2065-72
references.pmid: 20819928
references.citation: J Immunol. 2003 Jan 1;170(1):294-9
references.pmid: 12496412
references.citation: Blood. 2010 Feb 11;115(6):1166-74
references.pmid: 19903900
references.citation: Blood. 2010 Nov 11;116(19):3853-64
references.pmid: 20696944