Actin Regulatory Dynamics Required for T Cell Activation: A Quantitative and Systems-Level Perspective
type: CreativeWork
description: T cell activation occurs through interaction with an antigen-presenting cell (APC). Upon activation, signaling ensues with the coordination of dozens of diverse signaling molecules in space and time, a feature of cell signaling we call ‘spatiotemporal patterning’. We performed a systems-scale analysis of the spatiotemporal patterning of T cell signaling and have found that it is highly diverse. Over 50 signaling sensors were imaged in live primary T cells activated with APCs under various physiological stimulation conditions, and no two signaling intermediates showed the same dynamic localization. The activation environment controlled spatiotemporal features of T cell signaling and specific spatiotemporal features correlated with efficient T cell activation. To identify underlying cell biological mechanisms controlling spatiotemporal organization of signaling, we complimented our live cell imaging with microscopy across multiple scales and identified a dense transient F-actin network that extends from a highly interdigitated T cell:APC interface several micrometers deep into the T cell lamellum. Systems-scale imaging revealed a large network of proximal T cell signaling intermediates that localized to the lamellal actin network and shared the spatial, temporal, and mobility features of F-actin. Interference with lamellal actin dynamics modulated the activity of the associated proteins and impaired IL-2 production. These data strongly suggest that the transient deep F-actin network by controlling lamellal localization modulates the activity of a substantial part of the T cell signal transduction system. As a next step in understanding how spatiotemporal dynamics of signaling controls T cell activation, we have developed a quantitative 4D analysis approach for signaling networks and coupled it with traditional cell biological techniques to uncover higher order mechanisms of the control of actin dynamics by CD28 co-stimulation during T cell activation. A group of nine …
abstract: T cell activation occurs through interaction with an antigen-presenting cell (APC). Upon activation, signaling ensues with the coordination of dozens of diverse signaling molecules in space and time, a feature of cell signaling we call ‘spatiotemporal patterning’. We performed a systems-scale analysis of the spatiotemporal patterning of T cell signaling and have found that it is highly diverse. Over 50 signaling sensors were imaged in live primary T cells activated with APCs under various physiological stimulation conditions, and no two signaling intermediates showed the same dynamic localization. The activation environment controlled spatiotemporal features of T cell signaling and specific spatiotemporal features correlated with efficient T cell activation. To identify underlying cell biological mechanisms controlling spatiotemporal organization of signaling, we complimented our live cell imaging with microscopy across multiple scales and identified a dense transient F-actin network that extends from a highly interdigitated T cell:APC interface several micrometers deep into the T cell lamellum. Systems-scale imaging revealed a large network of proximal T cell signaling intermediates that localized to the lamellal actin network and shared the spatial, temporal, and mobility features of F-actin. Interference with lamellal actin dynamics modulated the activity of the associated proteins and impaired IL-2 production. These data strongly suggest that the transient deep F-actin network by controlling lamellal localization modulates the activity of a substantial part of the T cell signal transduction system. As a next step in understanding how spatiotemporal dynamics of signaling controls T cell activation, we have developed a quantitative 4D analysis approach for signaling networks and coupled it with traditional cell biological techniques to uncover higher order mechanisms of the control of actin dynamics by CD28 co-stimulation during T cell activation. A group of nine …
author: Roybal, Kole Thomas 1982-
language: en
keywords: Actins, Signal Transduction, T-Lymphocytes
date published: 2015-06-01T20:10:08Z
date modified: 2026-07-24T05:52:20Z
provider: University of Texas Southwestern Medical Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Texas Southwestern Medical Center

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property ID: Handle
value: https://hdl.handle.net/2152.5/ETD-UTSWMED-2013-05-91

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property ID: Handle
value: https://hdl.handle.net/2152.5/1587