Premium
Crtam regulates a late phase of T cell polarity and IFNγ/IL22 cytokine production
Author(s) -
YEH JUNGHUA,
Sidhu Sachdev S.,
Chan Andrew C.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.384
Subject(s) - microbiology and biotechnology , immunological synapse , t cell , cell polarity , cell growth , cdc42 , biology , signal transduction , t cell receptor , cell , immune system , immunology , biochemistry
T‐cell activation by antigen presenting cells requires the formation of an immunological synapse and the re‐organization of the signaling scaffold toward the T‐cell receptor contact region to generate second messengers required for efficient T cell effector functions. We have discovered that Crtam (class‐I MHC‐restricted T‐cell associated molecule), an Ig‐superfamily transmembrane protein upregulated during T cell activation, is required for T cells to establish a latter phase of cellular polarity, control proliferation and promote selective synthesis of IFNγ and IL22. Upregulated Crtam recruits the Scrib tumor‐suppressor and coordinates the assembly of a Cdc42/PKCζ containing complex at the leading edge of T cells >6 hours following the initiation of T cell activation. T cells lacking Crtam or expressing mutant Crtam unable to interact with Scrib, demonstrate normal early TCR‐mediated signaling, IS formation and actin polymerization, but are unable to maintain late T cell polarity, regulate cellular proliferation and have compromised IFNγ and IL22 synthesis. Moreover, forced expression of Crtam confers upon Crtam − T cells the ability to control cellular proliferation and gain IFNγ and IL22 production. These results reveal a distinct set of molecules regulate cell polarity during the late phases of T cell activation that impact cellular division, proliferation and selective cytokine production.