Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse.

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 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.

journal_name

Cell

journal_title

Cell

authors

Sims TN,Soos TJ,Xenias HS,Dubin-Thaler B,Hofman JM,Waite JC,Cameron TO,Thomas VK,Varma R,Wiggins CH,Sheetz MP,Littman DR,Dustin ML

doi

10.1016/j.cell.2007.03.037

subject

Has Abstract

pub_date

2007-05-18 00:00:00

pages

773-85

issue

4

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(07)00453-9

journal_volume

129

pub_type

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