Mechanobiological control of T-cell activation

“Actin dynamics are essential for immune cell activation. Using a suite of advanced quantitative methodologies to analyse resting and activated T cells, we demonstrate activating T cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse (IS). We show evidence that the kinetics of the antigen engaging the T-cell receptor controls the nanoscale actin organisation and mechanics of the IS. Using an engineered T-cell system expressing a specific T-cell receptor and stimulated by a range of antigens, force measurements revealed that the peak force experienced by the T-cell receptor during activation was independent of the kinetics of the stimulating antigen. Conversely, quantification of the actin retrograde flow velocity at the IS revealed a striking dependence on the antigen kinetics. Taken together, these findings suggest that the dynamics of the actin cytoskeleton actively adjusted to normalise 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 length- and time-scale of T-cell receptor signalling.”

Marco Fritzsche, Weatherall Institute of Molecular Medicine, Kennedy Institute, University of Oxford