Colin-York, H;
Javanmardi, Y;
Skamrahl, M;
Kumari, S;
Chang, VT;
Khuon, S;
Taylor, A;
... Fritzsche, M; + view all
(2019)
Cytoskeletal Control of Antigen-Dependent T Cell Activation.
Cell Reports
, 26
(12)
3369-3379.e5.
10.1016/j.celrep.2019.02.074.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Cytoskeletal Control of Antigen-Dependent T Cell Activation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2019.02.074 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2019.02.074 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | TFMactin dynamicsTCR clusterimmunological synapsemechanosensationmechanosensitivityT cell activation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10070665 |
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