1. Academic Validation
  2. The modulation of CD40 ligand signaling by transmembrane CD28 splice variant in human T cells

The modulation of CD40 ligand signaling by transmembrane CD28 splice variant in human T cells

  • J Exp Med. 2004 Apr 5;199(7):1025-31. doi: 10.1084/jem.20031705.
Sebastian A Mikolajczak 1 Bruce Y Ma Tetsuya Yoshida Ryoko Yoshida David J Kelvin Atsuo Ochi
Affiliations

Affiliation

  • 1 University Health Network, Toronto, Ontario M5G 2C4, Canada.
Abstract

The role of CD40 Ligand (CD40L)/CD40 signaling in T cell-dependent 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 kappaB activation. These data indicate that CD28i, by functioning as a signaling adaptor, transduces CD40L signaling as well as CD28 signaling in human T cells.

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