title: Binding of monoclonal antibody to CD16 causes calcium mobilization in large granular lymphocytes but inhibits NK killing.
abstract: A monoclonal antibody (mAb), CLB/FcR gran I, reactive with the CD16 Fc receptor (FcRlo/FcRIII) of human cells, leads to calcium mobilization in large granular lymphocytes (LGL) but not in granulocytes. Identical responses are obtained with F(ab')2 fragments of this antibody, indicating that the response is independent of Fc-FcR binding, and that bivalent cross-linking of this receptor is adequate for optimal calcium mobilization. The calcium response was greater in CD3- LGL compared to CD3+ LGL, although the response was augmented in the latter cells by prior rosetting with sheep red blood cells (SRBC). Calcium mobilization in CD3- LGL induced by CLB/FcR gran I is associated with inhibition of natural killer cell (NK) killing, and inhibition of the enhanced NK killing induced by the anti-CD2 low-density monoclonal antibody, 9.1. This supports the view that the NK-enhancing activity of 9.1 is due to simultaneous binding to CD2 and CD16, and may in fact be transduced through the CD16 molecule. The variable reported effects of anti-CD16 antibodies on NK killing are likely to reflect the epitope bound rather than the isotype of antibody used, since F(ab')2 fragments of CLB/FcR gran I also inhibit NK killing.
authors.affiliation: Department of Haematology, Middlesex University College Hospitals, London U.K.
authors.forename: E A
authors.initials: EA
authors.lastname: Macintyre
authors.forename: D W
authors.initials: DW
authors.lastname: Wallace
authors.forename: K
authors.initials: K
authors.lastname: O'Flynn
authors.forename: R
authors.initials: R
authors.lastname: Abdul-Gaffar
authors.forename: P A
authors.initials: PA
authors.lastname: Tetteroo
authors.forename: G
authors.initials: G
authors.lastname: Morgan
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018801:CD2 Antigens; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D002118:Calcium