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 journalArticle

    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 - Jan 1 1995

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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  • Cite this

    Truitt, K. E., Shi, J., Gibson, S., Segal, L. G., Mills, G. B., & Imboden, J. B. (1995). CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase. Journal of Immunology, 155(10), 4702-4710.