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Address correspondence to Atsuo Ochi, University Health Network, 200 Elizabeth St., MBRC-SR425, Toronto, Ontario M5G 2C4, Canada. Phone: (416) 340-4800; Fax: (416) 340-4596; email: aochi{at}uhnresearch.ca
The role of CD40 ligand (CD40L)/CD40 signaling in T celldependent B cell differentiation and maturation has been amply documented. The mechanism of CD40 signaling in B cells has been well established, whereas the signaling mechanism of CD40L in T cell costimulation remains unknown. In this study we show that CD28i, a transmembrane splice variant of CD28 costimulatory receptor, complexes with CD40L in human T cells. The cross-linking of CD40L resulted in the coendocytosis of CD28i with CD40L. The tyrosine phosphorylation of CD28i followed the cross-linking of CD40L, and the overexpression of CD28i augmented the c-Jun NH2-terminal kinase, p21-activated kinase 2, and nuclear factor
B activation. These data indicate that CD28i, by functioning as a signaling adaptor, transduces CD40L signaling as well as CD28 signaling in human T cells.
Key Words: CD40L CD28 CD28 variant T cell costimulation
B.Y. Ma's present address is Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
T. Yoshida's and R. Yoshida's present address is First Department of Internal Medicine, School of Medicine, Fukuoka University, Nanakuma 7-45-1, Jonan-Ku, Fukuoka 814-0180, Japan.
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