title: Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells.
abstract: 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.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA. lk2141@columbia.edu.
authors.forename: Erdem
authors.initials: E
authors.lastname: Tabdanov
authors.forename: Sasha
authors.initials: S
authors.lastname: Gondarenko
authors.forename: Sudha
authors.initials: S
authors.lastname: Kumari
authors.forename: Anastasia
authors.initials: A
authors.lastname: Liapis
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
authors.forename: Lance C
authors.initials: LC
authors.lastname: Kam
authors.forename: Thomas
authors.initials: T
authors.lastname: Iskratsch
mesh_terms: D000199:Actins / Q000502:physiology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001696:Biomechanical Phenomena; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D054992:Immunological Synapses / Q000502:physiology; D008024:Ligands; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell