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 P. Sheetz; Dan R. Littman; Michael L. Dustin

doi:10.1016/j.cell.2007.03.037

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 P. Sheetz, Dan R. Littman, Michael L. Dustin

Research output: Contribution to journal › Article › peer-review

287 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 language	English (US)
Pages (from-to)	773-785
Number of pages	13
Journal	Cell
Volume	129
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2007.03.037
State	Published - May 18 2007
Externally published	Yes

Keywords

CELLBIO
CELLIMMUNO

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2007.03.037

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@article{7a2a1b00cfef4c5792d678308152987d,

title = "Opposing Effects of PKCθ 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 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.",

keywords = "CELLBIO, CELLIMMUNO",

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

note = "Funding Information: We thank M. Nussenzweig for the CD11c + -YFP mice; and V. Nussenzweig for the WASp −/− mice; H.-G. Doebereiner, M. Brown, P. Ohashi and A. Douglass for helpful discussion; and T. Starr, T. Wu, and H. Patel for technical assistance. T.N.S. was supported in part through a National Psoriasis Foundation/USA seed grant and a National Institute of Allergy and Infectious Diseases (NIAID) AIDS Institutional Training Grant. T.J.S. was supported by a NIAID AIDS Institutional Training Grant. R.V. was supported by a Bernard Levine Fellowship. M.P.S., D.R.L. and M.L.D. were supported by the National Institutes of Health. M.L.D. was supported by the Irene Diamond Foundation. D.R.L. is an investigator of the Howard Hughes Medical Institute. ",

year = "2007",

month = may,

day = "18",

doi = "10.1016/j.cell.2007.03.037",

language = "English (US)",

volume = "129",

pages = "773--785",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Opposing Effects of PKCθ and WASp on Symmetry Breaking and Relocation of the Immunological Synapse

AU - Sims, Tasha N.

AU - Soos, Timothy J.

AU - Xenias, Harry S.

AU - Dubin-Thaler, Benjamin

AU - Hofman, Jake M.

AU - Waite, Janelle C.

AU - Cameron, Thomas O.

AU - Thomas, V. Kaye

AU - Varma, Rajat

AU - Wiggins, Chris H.

AU - Sheetz, Michael P.

AU - Littman, Dan R.

AU - Dustin, Michael L.

N1 - Funding Information: We thank M. Nussenzweig for the CD11c + -YFP mice; and V. Nussenzweig for the WASp −/− mice; H.-G. Doebereiner, M. Brown, P. Ohashi and A. Douglass for helpful discussion; and T. Starr, T. Wu, and H. Patel for technical assistance. T.N.S. was supported in part through a National Psoriasis Foundation/USA seed grant and a National Institute of Allergy and Infectious Diseases (NIAID) AIDS Institutional Training Grant. T.J.S. was supported by a NIAID AIDS Institutional Training Grant. R.V. was supported by a Bernard Levine Fellowship. M.P.S., D.R.L. and M.L.D. were supported by the National Institutes of Health. M.L.D. was supported by the Irene Diamond Foundation. D.R.L. is an investigator of the Howard Hughes Medical Institute.

PY - 2007/5/18

Y1 - 2007/5/18

N2 - 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.

AB - 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.

KW - CELLBIO

KW - CELLIMMUNO

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UR - http://www.scopus.com/inward/citedby.url?scp=34249013684&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2007.03.037

DO - 10.1016/j.cell.2007.03.037

M3 - Article

C2 - 17512410

AN - SCOPUS:34249013684

SN - 0092-8674

VL - 129

SP - 773

EP - 785

JO - Cell

JF - Cell

IS - 4

ER -

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

Abstract

Keywords

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