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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References
The Immunological Synapse: A Molecular Machine Controlling T Cell Activation
Arash Grakoui,Shannon K. Bromley,Cenk Sumen,Mark M. Davis,Andrey S. Shaw,Paul M. Allen,Michael L. Dustin +6 more
TL;DR: Immunological synapse formation is now shown to be an active and dynamic mechanism that allows T cells to distinguish potential antigenic ligands and was a determinative event for T cell proliferation.
3.2K
Three-dimensional segregation of supramolecular activation clusters in T cells
TL;DR: The three-dimensional distribution of receptors and intracellular proteins that cluster at the contacts between T cells and APCs during antigen-specific interactions, Surprisingly, instead of showing uniform oligomerization, these proteins clustered into segregated three- dimensional domains within the cell contacts.
2.4K
Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase Inhibitor STUDY OF Lck- AND FynT-DEPENDENT T CELL ACTIVATION
Jeffrey Herbert Hanke,Joseph P. Gardner,Robert L. Dow,Paul S. Changelian,William H. Brissette,Weringer Elora Jeanne,Brian A. Pollok,Patricia A. Connelly +7 more
TL;DR: This compound offers a useful new tool for examining the role of the Lck and FynT tyrosine kinases versus ZAP-70 in T cell activation as well as the roles of other Src family kinases in receptor function.
2K
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TL;DR: It is shown that T cells expressing the CD4 antigen respond with transient calcium signalling to even a single agonist peptide–MHC ligand, and that the organization of molecules in the contact zone of the T cell and APC takes on the characteristics of an immunological synapse when only about ten agonists are present.
873
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TL;DR: This chapter considers four aspects of the immunological synapse: the role of migration and stop signals, therole of the cytoskeleton, the roles of self-antigenic complexes, and the roleof second signals.