title: The interaction between CD300a and phosphatidylserine inhibits tumor cell killing by NK cells.
abstract: The activity of NK cells is controlled by inhibitory and activating receptors. The inhibitory receptors interact mostly with MHC class I proteins, however, inhibitory receptors such as CD300a, which bind to non-MHC class I ligands, also exist. Recently, it was discovered that phosphatidylserine (PS) is a ligand for CD300a and that the interaction between PS expressed on apoptotic cells and CD300a inhibits the uptake of apoptotic cells by phagocytic cells. Whether PS can inhibit NK-cell activity through CD300a is unknown. Here, we have generated specific antibodies directed against CD300a and we used these mAbs to demonstrate that various NK-cell clones express different levels of CD300a. We further demonstrated that both CD300a and its highly homologous molecule CD300c bind to the tumor cells equally well and that they recognize PS and additional unknown ligand(s) expressed by tumor cells. Finally, we showed that blocking the PS-CD300a interaction resulted in increased NK-cell killing of tumor cells. Collectively, we demonstrate a new tumor immune evasion mechanism that is mediated through the interaction between PS and CD300a and we suggest that CD300c, similarly to CD300a, also interacts with PS.
authors: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute, Hadassah Medical School, The Hebrew University, Jerusalem, Israel.
authors: Dikla
authors: D
authors: Lankry
authors: Tihana Lenac
authors: TL
authors: Rovis
authors: Stipan
authors: S
authors: Jonjic
authors: Ofer
authors: O
authors: Mandelboim
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D019139:Tumor Escape
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C515070:CD300A protein, human; C444139:CD300C protein, human; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D010718:Phosphatidylserines; D011971:Receptors, Immunologic
keywords: CD300; Ligand; Phosphtidylserine; Tumor cell
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