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Spatiotemporal patterning of T cell signaling as an important regulator of T cell activation at the systems level
Author(s) -
Wuelfing Christoph,
Singleton Kentner L.,
Roybal Kole T.,
Sun Yi
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.22.1_supplement.1064.16
Subject(s) - regulator , immunological synapse , microbiology and biotechnology , negative regulator , cell signaling , signal transduction , t cell receptor , cell , biology , t cell , chemistry , genetics , immune system , gene
Spatiotemporal patterning of various individual proteins in T cell activation, i.e. the formation of an immunological synapse, is well described. However, a comprehensive analysis of multiple proteins in the same system is still lacking, yet critical: Spatiotemporal patterning governs interaction probabilities. Two proteins enriched at the same time and location are more likely to interact than ones with distinct patterns. To thus understand how spatiotemporal patterning guides signaling interactions, we determined the patterning of 25 elements of T cell activation, mostly signaling intermediates, in the activation of the same primary T cells by professional APCs. Spatiotemporal pattering was highly diverse: No two elements of T cell activation showed the same patterns. This diversity is critical in allowing control of spatiotemporal patterning to be a powerful regulator of T cell signaling. We also determined the patterning of key receptors/signaling intermediates using T cells with different TCRs. Here, TCR patterning controlled patterning and efficiency of T cell signaling. Spatiotemporal pattering thus is an important regulator of T cell signaling at the systems level. Supported by the NIH.