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 M(r) 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.
Mishra
B B
BB
Department of Neurology, Temple University Hospital, Philadelphia, Pennsylvania 19140.
Fernandes
A M
AM
Blaese
R M
RM
Muchmore
A V
AV
D015153:Blotting, Western; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D006801:Humans; D007553:Isotope Labeling; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000378:metabolism* / Q000494:pharmacology; D009088:Mucoproteins / Q000378:metabolism* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D058949:Uromodulin
D002352:Carrier Proteins; D008934:Mitogens; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin