Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

T cell receptor (TCR) activation and signaling precede immunological synapse formation and are sustained for hours after initiation. However, the precise physical sites of the initial and sustained TCR signaling are not definitively known. We report here that T cell activation was initiated and sustained in TCR-containing microclusters generated at the initial contact sites and the periphery of the mature immunological synapse. Microclusters containing TCRs, the tyrosine kinase Zap70 and the adaptor molecule SLP-76 were continuously generated at the periphery. TCR microclusters migrated toward the central supramolecular cluster, whereas Zap70 and SLP-76 dissociated from these microclusters before the microclusters coalesced with the TCR-rich central supramolecular cluster. Tyrosine phosphorylation and calcium influx were induced as microclusters formed at the initial contact sites. Inhibition of signaling prevented recruitment of Zap70 into the microclusters. These results indicated that TCR-rich microclusters initiate and sustain TCR signaling.

Original publication

DOI

10.1038/ni1272

Type

Journal article

Journal

Nat Immunol

Publication Date

12/2005

Volume

6

Pages

1253 - 1262

Keywords

Adaptor Proteins, Signal Transducing, Animals, Cells, Cultured, Genes, Reporter, Lymphocyte Activation, Mice, Mice, Inbred C3H, Phosphoproteins, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, T-Lymphocytes, ZAP-70 Protein-Tyrosine Kinase