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Engagement of T cell receptor triggers its recruitment to low‐density detergent‐insoluble membrane domains
Author(s) -
Montixi Christine,
Langlet Claire,
Bernard AnneMarie,
Thimonier Jean,
Dubois Catherine,
Wurbel MarcAndré,
Chauvin JeanPaul,
Pierres Michel,
He HaiTao
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.18.5334
Subject(s) - t cell receptor , biology , cd3 , phosphorylation , microbiology and biotechnology , tyrosine phosphorylation , tyrosine kinase , proto oncogene tyrosine protein kinase src , signal transduction , receptor tyrosine kinase , kinase , tyrosine , sh3 domain , receptor , src family kinase , t cell , biochemistry , antigen , cd8 , immunology , immune system
T‐cell receptors (TCRs) upon binding to peptide–MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (γδϵ) and ζ subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP‐70 kinase and other signaling components. We examined the role of the low‐density detergent‐insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine‐phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM‐associated receptor complexes are highly enriched in the hyperphosphorylated p23 ζ chains, contain most of the TCR/CD3‐associated, phosphorylation‐activated ZAP‐70 kinases and seem to integrate into higher order, multiple tyrosine‐phosphorylated substrate‐containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.