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Cytoskeletal actin dynamics is essential for T cell activation. Here, we show evidence that the binding kinetics of the antigen engaging the T cell receptor influences the nanoscale actin organization and mechanics of the immune synapse. Using an engineered T cell system expressing a specific T cell receptor and stimulated by a range of antigens, we found that the peak force experienced by the T cell receptor during activation was independent of the unbinding kinetics of the stimulating antigen. Conversely, quantification of the actin retrograde flow velocity at the synapse revealed a striking dependence on the antigen unbinding kinetics. These findings suggest that the dynamics of the actin cytoskeleton actively adjusted to normalize the force experienced by the T cell receptor in an antigen-specific manner. Consequently, tuning actin dynamics in response to antigen kinetics may thus be a mechanism that allows T cells to adjust the lengthscale and timescale of T cell receptor signaling. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.


Huw Colin-York, Yousef Javanmardi, Mark Skamrahl, Sudha Kumari, Veronica T Chang, Satya Khuon, Aaron Taylor, Teng-Leong Chew, Eric Betzig, Emad Moeendarbary, Vincenzo Cerundolo, Christian Eggeling, Marco Fritzsche. Cytoskeletal Control of Antigen-Dependent T Cell Activation. Cell reports. 2019 Mar 19;26(12):3369-3379.e5

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PMID: 30893608

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