The LLT1 receptor induces IFN-gamma production by human natural killer cells.
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.
Mathew
Porunelloor A
PA
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
Chuang
Samuel S
SS
Vaidya
Swapnil V
SV
Kumaresan
Pappanaicken R
PR
Boles
Kent S
KS
Pham
Hoang-Tuan K
HT
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*
D000911:Antibodies, Monoclonal; C400041:CLEC2D protein, human; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D007371:Interferon-gamma