Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse.
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.
Sims
Tasha N
TN
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
Soos
Timothy J
TJ
Xenias
Harry S
HS
Dubin-Thaler
Benjamin
B
Hofman
Jake M
JM
Waite
Janelle C
JC
Cameron
Thomas O
TO
Thomas
V Kaye
VK
Varma
Rajat
R
Wiggins
Chris H
CH
Sheetz
Michael P
MP
Littman
Dan R
DR
Dustin
Michael L
ML
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004794:Enzyme Repression / Q000187:drug effects / Q000502:physiology; D007365:Intercellular Junctions / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008563:Membrane Lipids; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta