Inhibition of the function of the FcgammaRIIB by a monoclonal antibody to thymic shared antigen-1, a Ly-6 family antigen.
Thymic shared antigen-1 (TSA-1) is a member of the Ly-6 family of glycosyl-phosphatidylinositol (GPI)-linked proteins. While it has been proposed that TSA-1 may play a role in thymic development, a physiological ligand for this antigen has not been identified. Here we report that a monoclonal antibody (mAb) to TSA-1, generated by immunizing a hamster with CD40 ligand (CD40L)-activated B cells, interferes with the function of FcgammaRIIB on splenic B cells and the B-cell lymphoma cell line, M12, by binding to TSA on the same cells. The interaction of anti-TSA with FcgammaRIIB resulted in an inhibition of the ability of the FcgammaRIIB to cross-link and/or aggregate soluble anti-CD3 or soluble anti-Cbeta T-cell receptor (TCR), leading to an inhibition of induction of expression of CD25 and CD69, interleukin (IL)-2 production and proliferation of naive T cells. Cross-blocking studies with mAbs strongly suggested that a physical association exists between TSA-1 and the FcgammaRIIB on the surface of activated B cells and favour the view that a functional intermolecular association exists between these two distinct membrane antigens.
Ding
L
L
Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20851-1448, USA. ding@cber.fda.gov
Shevach
E M
EM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D018929:Cell Culture Techniques; D006224:Cricetinae; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017452:Receptors, IgG / Q000037:antagonists & inhibitors* / Q000276:immunology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D008565:Membrane Proteins; D017452:Receptors, IgG; C084839:thymic shared antigen-1; D023201:CD40 Ligand