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CD28 and CTLA‐4 coreceptor expression and signal transduction
Author(s) -
Rudd Christopher E.,
Taylor Alison,
Schneider Helga
Publication year - 2009
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2009.00770.x
Subject(s) - cd28 , biology , t cell , signal transduction , microbiology and biotechnology , t cell receptor , cytotoxic t cell , pi3k/akt/mtor pathway , protein kinase b , ctla 4 , zap70 , grb2 , clonal anergy , cancer research , immunology , immune system , tyrosine kinase , biochemistry , in vitro
Summary: T‐cell activation is mediated by antigen‐specific signals from the TCRζ/CD3 and CD4–CD8–p56lck complexes in combination with additional co‐signals provided by coreceptors such as CD28, inducible costimulator (ICOS), cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), programmed death (PD‐1), and others. CD28 and ICOS provide positive signals that promote and sustain T‐cell responses, while CTLA‐4 and PD‐1 limit responses. The balance between stimulatory and inhibitory co‐signals determines the ultimate nature of T‐cell responses where response to foreign pathogen is achieved without excess inflammation and autoimmunity. In this review, we outline the current knowledge of the CD28 and CTLA‐4 signaling mechanisms [involving phosphatidylinositol 3 kinase (PI3K), growth factor receptor‐bound protein 2 (Grb2), Filamin A, protein kinase C θ (PKCθ), and phosphatases] that control T‐cell immunity. We also present recent findings on T‐cell receptor‐interacting molecule (TRIM) regulation of CTLA‐4 surface expression, and a signaling pathway involving CTLA‐4 activation of PI3K and protein kinase B (PKB)/AKT by which cell survival is ensured under conditions of anergy induction.