The formation of the immunological synapse between a T cell and the antigen-presenting cell (APC) is critically dependent on actin dynamics, downstream of T cell receptor (TCR) and integrin (LFA-1) signalling. There is also accumulating evidence that mechanical forces, generated by actin polymerization and/or myosin contractility regulate T cell signalling. Because both receptor pathways are intertwined, their contributions towards the cytoskeletal organization remain elusive. Here, we identify the specific roles of TCR and LFA-1 by using a combination of micropatterning to spatially separate signalling systems and nanopillar arrays for high-precision analysis of cellular forces. We identify that Arp2/3 acts downstream of TCRs to nucleate dense actin foci but propagation of the network requires LFA-1 and the formin FHOD1. LFA-1 adhesion enhances actomyosin forces, which in turn modulate actin assembly downstream of the TCR. Together our data shows a mechanically cooperative system through which ligands presented by an APC modulate T cell activation.
Integr Biol (Camb)
1272 - 1284
Actins, Antigen Presentation, Antigen-Presenting Cells, Biomechanical Phenomena, CD4-Positive T-Lymphocytes, Cell Adhesion, Cells, Cultured, Cytoskeleton, Humans, Immunological Synapses, Ligands, Lymphocyte Activation, Lymphocyte Function-Associated Antigen-1, Models, Immunological, Receptors, Antigen, T-Cell, Signal Transduction