Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.1039/c5ib00032g

Type

Journal article

Journal

Integr Biol (Camb)

Publication Date

10/2015

Volume

7

Pages

1272 - 1284

Keywords

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