title: Production and characterization of a novel monoclonal antibody inhibitory for murine natural killer cell activity.
abstract: Natural killer (NK) cells are considered to play an important role in tumor surveillance. The killing of tumor target cells by NK cells is the result of a complex series of sequential binding, signal processing and lytic events. However, the mechanism which NK cells use to recognize tumor targets is poorly understood. To further study the cell-surface molecules involved in tumor recognition, we immunized rats against cloned murine T cells with NK activity (DBA/2.1) and generated rat-mouse hybridomas which were screened for the ability to block lytic activity of DBA/2.1 effector cells. Culture supernatants from one IgM-producing hybridoma, designated S1C4, were found to consistently inhibit DBA/2.1-mediated lysis of YAC-1 target cells. Endogenous splenic NK activity was also diminished in the presence of S1C4 monoclonal antibody (mAb) while alloantigen-specific cytotoxic T lymphocyte (CTL) activity was not affected. S1C4 mAb appears to react with effector cell-surface structures involved in the recognition/adhesion phase of NK activity since pretreatment of effector cells with mAb S1C4 inhibits their ability to bind to YAC-1 target cells. ELISA studies revealed that the S1C4 antigen is expressed by a range of lymphoid cell lines, as well as by DBA/2.1 cells and fresh splenic NK cells. S1C4 mAb were shown to react with 22, 24, 30, and 46 kiloDalton (kDa) DBA/2.1 cell membrane components on immunoblots performed under reducing conditions. These structures do not correspond to any known recognition/adhesion molecules, suggesting that mAb S1C4 defines novel cell membrane components involved in NK cell function.
authors.affiliation: Department of Microbiology, Dalhousie University, Halifax, Nova Scotia.
authors.forename: D W
authors.initials: DW
authors.lastname: Hoskin
authors.forename: J C
authors.initials: JC
authors.lastname: Roder
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006825:Hybridomas / Q000276:immunology; D015151:Immunoblotting; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface