Characterization of T Cell Ligands for Uromodulin: A Possible Role in Costimulation

In this study, we demonstrate that uromodulin (UMN) is a costimulator of T cells and characterize the T cell ligand which might mediate its costimulatory effect. UMN is an 85-kDa human urinary glycoprotein which is better known for its ability to suppress antigen-induced proliferation of peripheral blood mononuclear cells. It also has a mitogenic effect on peripheral blood cells, which has not been investigated. In this study, costimulation of T cells by UMN is observed only in the absence of B cells and antigen-specific antiserum. Using ligand binding assays we also demonstrate a specific receptor for UMN on peripheral blood T cells and T cell lines (Kd of 10-8). We describe two uromodulin binding proteins of approximate Mt 35 and 55 kDa, isolated from detergent extract of T cells, either of which may represent a receptor for UMN or an associated signal transduction molecule involved in the stimulatory effect of UMN on T cells. Finally, we demonstrate a similar protein in a renal cell line, which may clarify the renal role of UMN.