Inhibition of the function of the Fc gamma RIIB 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 th is antigen has not been identified. Here we report that a monoclonal antibo dy (mAb) to TSA-1, generated by ininaunizing a hamster with CD40 ligand (CD 40L) -activated B cells, interferes with the function of Fc gamma RIIB on s plenic 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 agg regate soluble anti-CD3 or soluble anti-C beta T-cell receptor (TCR), leadi ng to an inhibition of induction of expression of CD25 and CD69, interleuki n (IL)-2 production and proliferation of naive T cells. Cross-blocking stud ies 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.