Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling.
TL;DR: T cell receptor (TCR) microclusters form within seconds of T cell contact with supported planar bilayers containing intercellular adhesion molecule-1 and agonist major histocompatibility complex (MHC)-peptide complexes, and elevation of cytoplasmic Ca2+ is observed within seconds after the first detectable micro-clusters as mentioned in this paper.
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Abstract: T cell receptor (TCR) microclusters form within seconds of T cell contact with supported planar bilayers containing intercellular adhesion molecule-1 and agonist major histocompatibility complex (MHC)-peptide complexes, and elevation of cytoplasmic Ca2+ is observed within seconds of the first detectable microclusters. At 0-30 s after contact, TCR microclusters are colocalized with activated forms of Lck, ZAP-70, and the linker for activation of T cells. By 2 min, activated kinases are reduced in the older central microclusters, but are abundant in younger peripheral microclusters. By 5 min, TCR in the central supramolecular activation cluster have reduced activated kinases, whereas faint peripheral TCR microclusters efficiently generated activated Lck and ZAP-70. TCR microcluster formation is resistant to inhibition by Src family kinase inhibitor PP2, but is abrogated by actin polymerization inhibitor latrunculin A. We propose that Src kinase-independent formation of TCR microclusters in response to agonist MHC-peptide provides an actin-dependent scaffold for signal amplification.
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Citations
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Microclusters as T Cell Signaling Hubs: Structure, Kinetics, and Regulation
TL;DR: In this article, the role of cell surface molecules in microcluster formation and the kinetics of molecular recruitment via intracellular vesicular trafficking to microclusters is described.
Reinforcement of integrin-mediated T-Lymphocyte adhesion by TNF-induced Inside-out Signaling.
TL;DR: Analysis of single-molecule ruptures demonstrates that TNF strengthens sub-cellular single rupture events at short cell-surface contact times, providing quantitative evidence for the significant impact of TNF-induced inside-out signaling in the T-lymphocyte initial adhesion machinery.
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Ultrasensitivity in the Cofilin Signaling Module: A Mechanism for Tuning T Cell Responses
TL;DR: This work proposes that bistability in the cofilin signaling module might be instrumental in T cell responses to antigenic stimulation, and discusses mechanisms that can potentially generate a bistable response in the phosphorylation/dephosphorylation monocycle that regulates the activity of coFilin in dynamic actin networks.
Ratiometric Imaging of the T-Cell Actin Cytoskeleton Reveals the Nature of Receptor-Induced Cytoskeletal Enrichment
Alexander A. Smoligovets,Alexander A. Smoligovets,Adam W. Smith,Adam W. Smith,Jay T. Groves,Jay T. Groves +5 more
TL;DR: The results suggest that TCR-associated actin consists of a relatively high proportion of the stable cytoskeletal fraction and extends away from the cell membrane into the cell, which implies that actin enrichment at mechanically trapped TCRs results from three-dimensional bunching of the existing filamentous actin network.
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