Opposing Effects of PKCθ and WASp on Symmetry Breaking and Relocation of the Immunological Synapse

Tasha N. Sims, Timothy J. Soos, Harry S. Xenias, Benjamin Dubin-Thaler, Jake M. Hofman, Janelle C. Waite, Thomas O. Cameron, V. Kaye Thomas, Rajat Varma, Chris H. Wiggins, Michael Sheetz, Dan R. Littman, Michael L. Dustin

Research output: Contribution to journalArticle

244 Scopus citations

Abstract

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 PKCθ, which is localized to the F-actin-dependent peripheral (p)SMAC. PKCθ-/- 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 PKCθ was inhibited. Thus, opposing effects of PKCθ and WASp control IS stability through pSMAC symmetry breaking and reformation.

Original languageEnglish (US)
Pages (from-to)773-785
Number of pages13
JournalCell
Volume129
Issue number4
DOIs
StatePublished - May 18 2007
Externally publishedYes

Keywords

  • CELLBIO
  • CELLIMMUNO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Sims, T. N., Soos, T. J., Xenias, H. S., Dubin-Thaler, B., Hofman, J. M., Waite, J. C., Cameron, T. O., Thomas, V. K., Varma, R., Wiggins, C. H., Sheetz, M., Littman, D. R., & Dustin, M. L. (2007). Opposing Effects of PKCθ and WASp on Symmetry Breaking and Relocation of the Immunological Synapse. Cell, 129(4), 773-785. https://doi.org/10.1016/j.cell.2007.03.037