Origin, Organization, Dynamics, and Function of Actin and Actomyosin Networks at the T Cell Immunological Synapse

The engagement of a T cell with an antigen-presenting cell (APC) or activating surface results in the formation within the T cell of several distinct actin and actomyosin networks. These networks reside largely within a narrow zone immediately under the T cell's plasma membrane at its site of contact with the APC or activating surface, i.e., at the immunological synapse. Here we review the origin, organization, dynamics, and function of these synapse-associated actin and actomyosin networks. Importantly, recent insights into the nature of these actin-based cytoskeletal structures were made possible in several cases by advances in light microscopy.

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Antithymocyte Globulin Impairs T-Cell/Antigen-Presenting Cell Interaction: Disruption of Immunological Synapse and Conjugate Formation

Transplantation Journal ◽

10.1097/01.tp.0000266677.45428.80 ◽

2007 ◽

Vol 84 (1) ◽

pp. 117-121 ◽

Cited By ~ 19

Author(s):

Michael Haidinger ◽

Ren?? Geyeregger ◽

Marko Poglitsch ◽

Thomas Weichhart ◽

Maximilian Zeyda ◽

...

Keyword(s):

T Cell ◽

Antithymocyte Globulin ◽

Immunological Synapse ◽

Cell Interaction ◽

Antigen Presenting Cell ◽

Cell Antigen ◽

Antigen Presenting

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Actin clearance promotes polarized dynein accumulation at the immunological synapse

10.1101/505990 ◽

2018 ◽

Cited By ~ 1

Author(s):

Elisa Sanchez ◽

Xin Liu ◽

Morgan Huse

Keyword(s):

T Cell ◽

Immunological Synapse ◽

Cell Receptor ◽

Actin Dynamics ◽

Synaptic Membrane ◽

Filamentous Actin ◽

Antigen Presenting Cell ◽

Imaging Methodology ◽

Antigen Presenting ◽

Cell Effector Function

Immunological synapse (IS) formation between a T cell and an antigen-presenting cell is accompanied by the reorientation of the T cell centrosome toward the interface. This polarization response is thought to enhance the specificity of T cell effector function by enabling the directional secretion of cytokines and cytotoxic factors toward the antigen-presenting cell. Centrosome reorientation is controlled by polarized signaling through diacylglycerol (DAG) and protein kinase C (PKC). This drives the recruitment of the motor protein dynein to the IS, where it pulls on microtubules to reorient the centrosome. Here, we used T cell receptor photoactivation and imaging methodology to investigate the mechanisms controlling dynein accumulation at the synapse. Our results revealed a remarkable spatiotemporal correlation between dynein recruitment to the synaptic membrane and the depletion of cortical filamentous actin (F-actin) from the same region, suggesting that the two events were causally related. Consistent with this hypothesis, we found that pharmacological disruption of F-actin dynamics in T cells impaired both dynein accumulation and centrosome reorientation. DAG and PKC signaling were necessary for synaptic F-actin clearance and dynein accumulation, while calcium signaling and microtubules were dispensable for both responses. Taken together, these data provide mechanistic insight into the polarization of cytoskeletal regulators and highlight the close coordination between microtubule and F-actin architecture at the IS.

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