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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A role for rebinding in rapid and reliable T cell responses to antigen
TL;DR: This theoretical study investigates the role of localized rebinding between a T cell receptor and an antigen and demonstrates that by allowing the signaling state of individual receptors to persist during brief unbinding events, T cells are able to discriminate antigens based on both their unbinding and rebinding rates.
Altered actin centripetal retrograde flow in physically restricted immunological synapses.
Cheng-han Yu,Cheng-han Yu,Hung-Jen Wu,Hung-Jen Wu,Yoshihisa Kaizuka,Yoshihisa Kaizuka,Ronald D. Vale,Ronald D. Vale,Jay T. Groves +8 more
TL;DR: Localized actin flow analysis reveals that, while there is no influence on actin motion from substrate patterns directly, velocity differences of actin are observed over physically trapped TCR clusters, consistent with a dynamic and dissipative coupling between T CR clusters and viscoelastic actin network.
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TL;DR: Using a variety of techniques, developed over the last decade, have allowed us to visualize and quantify key aspects of the dynamic synaptic interface and have furthered the authors' understanding of their function.
Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse.
Catherine A Hartzell,Katarzyna I. Jankowska,Katarzyna I. Jankowska,Janis K. Burkhardt,Janis K. Burkhardt,Richard S. Lewis +5 more
TL;DR: It is found that Ca2+ influx is required to drive actin organization and dynamics at the synapse, and potential feedback loops through which Ca2-dependent retrograde actin flow may modulate TCR signaling are revealed.
Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands.
Philippe Robert,Milos Aleksic,Omer Dushek,Vincenzo Cerundolo,Pierre Bongrand,P. Anton van der Merwe +5 more
TL;DR: For the first time to the authors' knowledge, the two-dimensional binding properties of eight TCR/pMHC couples in a cell-free system with single bond resolution are reported, suggesting possible refinements of contemporary models of signal generation by T cell receptors.
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