Cytoskeletal control of antigen-dependent T cell activation

Journal article

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.

Authors: Colin-York, H; Javanmardi, Y; Skamrahl, M; Kumari, S; Chang, V

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell Reports
• Volume: 26
• Issue: 12
• Pages: 3369-3379
• Publication date: 2019-03-19
• Acceptance date: 2019-02-20
• DOI: 10.1016/j.celrep.2019.02.074
• ISSN: 2211-1247
• Keywords: mechanosensation; actin dynamics; TFM; immunological synapse; mechanosensitivity; FFR; T cell activation; TCR cluster