CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase

K. E. Truitt, J. Shi, S. Gibson, L. G. Segal, G. B. Mills, J. B. Imboden

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

CD28, a cell-surface molecule expressed by T cells, delivers costimulatory signals during the activation of T cells by Ag. Stimulation of CD28 induces its association with phosphatidylinositol 3'-kinase (PI3-K), raising the possibility that PI3-K plays a critical role in CD28 signaling. We find, however, that wortmannin, a potent inhibitor of PI3-K, does not block CD28- mediated costimulation of Jurkat (a human T cell line) or of murine CD4+ T cells. To address further the role of PI3-K in CD28-mediated signaling, we expressed mutant murine CD28 molecules in Jurkat cells. Mutation of Tyr 170 of murine CD28 to Phe abrogates the association of murine CD28 with PI3-K but does not affect the ability of murine CD28 to augment IL-2 production by Jurkat cells in response to the combination of ionomycin and PMA. Conversely, a mutant of murine CD28 that has a Tyr at position 170 but has Phe substitutions at the remaining three cytoplasmic tyrosines retains the ability to associate with PI3-K and has an impaired ability to deliver a costimulus that augments IL-2 production. CD28, therefore, can deliver costimulatory signals independently of its interaction with PI3-K, and association with PI3-K is insufficient to mediate the full effector function of CD28. Optimal signaling by CD28 requires the integrity of one or more of the carboxyl-terminal three Tyr residues.

Original languageEnglish (US)
Pages (from-to)4702-4710
Number of pages9
JournalJournal of Immunology
Volume155
Issue number10
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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