Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling.

Journal article

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.

Authors: Campi, G; Varma, R; Dustin, M

• Journal: Journal of experimental medicine
• Volume: 202
• Issue: 8
• Pages: 1031-1036
• Publication date: 2005-10-01
• DOI: 10.1084/jem.20051182
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Signal Transduction; Actins; T-Lymphocytes; Receptors, Antigen, T-Cell; Mice, Transgenic; Calcium; Intercellular Adhesion Molecule-1; Animals; Time Factors; Cells, Cultured; Major Histocompatibility Complex; Mice