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The immunological synapse (IS) is a junction between the T cell and antigen-presenting cell and is composed of supramolecular activation clusters (SMACs). No studies have been published on naive T cell IS dynamics. Here, we find that IS formation during antigen recognition comprises cycles of stable IS formation and autonomous naive T cell migration. The migration phase is driven by PKCtheta, which is localized to the F-actin-dependent peripheral (p)SMAC. PKCtheta(-/-) T cells formed hyperstable IS in vitro and in vivo and, like WT cells, displayed fast oscillations in the distal SMAC, but they showed reduced slow oscillations in pSMAC integrity. IS reformation is driven by the Wiscott Aldrich Syndrome protein (WASp). WASp(-/-) T cells displayed normal IS formation but were unable to reform IS after migration unless PKCtheta was inhibited. Thus, opposing effects of PKCtheta and WASp control IS stability through pSMAC symmetry breaking and reformation.

Original publication

DOI

10.1016/j.cell.2007.03.037

Type

Journal article

Journal

Cell

Publication Date

05/2007

Volume

129

Pages

773 - 785

Addresses

Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.

Keywords

Antigen-Presenting Cells, T-Lymphocytes, Intercellular Junctions, Animals, Mice, Knockout, Mice, Isoenzymes, Protein Kinase C, Membrane Lipids, Enzyme Inhibitors, Lymphocyte Activation, Cell Communication, Cell Movement, Antigen Presentation, Enzyme Repression, Enzyme Activation, Wiskott-Aldrich Syndrome Protein