Cytoskeletal Control of Antigen-Dependent T Cell Activation

Summary: 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. : T cell activation relies on a dynamic actin cytoskeleton. Here, Colin-York et al. show how the kinetics of the stimulating antigen influence the dynamics of actin. This feedback mechanism influences the mechanics at the immune synapse, allowing T cells to orchestrate the length scale and timescale of signaling. Keywords: TFM, actin dynamics, TCR cluster, immunological synapse, mechanosensation, mechanosensitivity, T cell activatio