Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling.
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.
Campi
Gabriele
G
Department of Pathology and the Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA.
Varma
Rajat
R
Dustin
Michael L
ML
D000199:Actins / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors
D000199:Actins; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1; D002118:Calcium