title: The LLT1 receptor induces IFN-gamma production by human natural killer cells.
abstract: Natural killer cell functions are regulated by signals through activating and inhibitory receptors. These receptors belong to the immunoglobulin superfamily or the lectin superfamily. We have previously identified a lectin-like transcript, LLT1, expressed in human NK cells. In the present study, we have generated a monoclonal antibody, L9.7, that specifically binds LLT1 receptor and studied the functional role of LLT1 in human NK cells. Binding of mAb L9.7 to surface LLT1 induced IFN-gamma production, but did not modulate cytotoxicity by YT cells, a human NK cell line. We further demonstrate that in resting NK cells as well as in IL-2 activated NK cells LLT1 induced IFN-gamma production, but not cytotoxicity. Excess amounts of L9.7 mAb failed to increase natural or antibody-dependent cell-mediated cytolytic activity, whereas minimal amounts achieved maximal production of IFN-gamma by YT and activated NK cells. These findings further support the separation of signaling pathways that regulate cytotoxicity and IFN-gamma production in resting as well as activated NK cells.
authors.affiliation: Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA. pmathew@hsc.unt.edu
authors.forename: Porunelloor A
authors.initials: PA
authors.lastname: Mathew
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Chuang
authors.forename: Swapnil V
authors.initials: SV
authors.lastname: Vaidya
authors.forename: Pappanaicken R
authors.initials: PR
authors.lastname: Kumaresan
authors.forename: Kent S
authors.initials: KS
authors.lastname: Boles
authors.forename: Hoang-Tuan K
authors.initials: HT
authors.lastname: Pham
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D019281:Dimerization; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; C400041:CLEC2D protein, human; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D007371:Interferon-gamma