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The actin-driven spatiotemporal organization of T-cell signaling at the system scale

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)133-147
Number of pages15
JournalImmunological Reviews
Volume256
Issue number1
Early online date10 Oct 2013
DOIs
DateE-pub ahead of print - 10 Oct 2013
DatePublished (current) - Nov 2013

Abstract

T cells are activated through interaction with antigen-presenting cells (APCs). During activation, receptors and signaling intermediates accumulate in diverse spatiotemporal distributions. These distributions control the probability of signaling interactions and thus govern information flow through the signaling system. Spatiotemporally resolved system-scale investigation of signaling can extract the regulatory information thus encoded, allowing unique insight into the control of T-cell function. Substantial technical challenges exist, and these are briefly discussed herein. While much of the work assessing T-cell spatiotemporal organization uses planar APC substitutes, we focus here on B-cell APCs with often stark differences. Spatiotemporal signaling distributions are driven by cell biologically distinct structures, a large protein assembly at the interface center, a large invagination, the actin-supported interface periphery as extended by smaller individual lamella, and a newly discovered whole-interface actin-driven lamellum. The more than 60 elements of T-cell activation studied to date are dynamically distributed between these structures, generating a complex organization of the signaling system. Signal initiation and core signaling prefer the interface center, while signal amplification is localized in the transient lamellum. Actin dynamics control signaling distributions through regulation of the underlying structures and drive a highly undulating T-cell/APC interface that imposes substantial constraints on T-cell organization. We suggest that the regulation of actin dynamics, by controlling signaling distributions and membrane topology, is an important rheostat of T-cell signaling.

    Research areas

  • Actins, Animals, Antigen-Presenting Cells, Cell Communication, Humans, Lymphocyte Activation, Signal Transduction, T-Lymphocytes, T-cell signaling, Systems biology, Imaging, Actin

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  • Immunological Reviews - Accepted Manuscript

    Rights statement: This is the peer reviewed version of the following article: Roybal, K. T., Sinai, P., Verkade, P., Murphy, R. F. and Wülfing, C. (2013), The actin-driven spatiotemporal organization of T-cell signaling at the system scale. Immunological Reviews, 256: 133–147, which has been published in final form at DOI: doi: 10.1111/imr.12103. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

    Accepted author manuscript, 4 MB, PDF document

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