Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells

Journal article

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.

Authors: Tabdanov, E; Gondarenko, S; Kumari, S; Liapis, A; Dustin, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Royal Society of Chemistry
• Journal: Integrative Biology
• Volume: 7
• Issue: 10
• Pages: 1272-1284
• Publication date: 2015-07-09
• Acceptance date: 2015-07-01
• DOI: 10.1039/c5ib00032g
• EISSN: 1757-9708
• ISSN: 1757-9694
• Language: English