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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.

Original publication




Journal article


Integrative biology : quantitative biosciences from nano to macro

Publication Date





1272 - 1284


Department of Biomedical Engineering, Columbia University, New York, NY, USA.


Antigen-Presenting Cells, CD4-Positive T-Lymphocytes, Cells, Cultured, Cytoskeleton, Humans, Actins, Lymphocyte Function-Associated Antigen-1, Receptors, Antigen, T-Cell, Ligands, Lymphocyte Activation, Cell Adhesion, Signal Transduction, Antigen Presentation, Models, Immunological, Immunological Synapses, Biomechanical Phenomena