Inhibition of the function of the FcγRIIB 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 ininaunizing a hamster with CD40 ligand (CD40L) -activated B cells, interferes with the function of Fc gamma RIIB 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 Fc gamma RIIB resulted in an inhibition of the ability of the Fc gamma RIIB to cross-link and/or aggregate soluble anti-CD3 or soluble anti-C beta 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 Fc gamma RIIB on the surface of activated B cells and favour the view that a functional intermolecular association exists between these two distinct membrane antigens.