Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact

• Sudha Kumari ^[2] ; Michael Mak ^[3] ; Yeh‐Chuin Poh ^[4] ; Mira Tohme ^[5] ; Nicki Watson ^[6] ; Mariane Melo ^[2] ; Erin Janssen ^[5] ; Michael Dustin ^[1] ; Raif Geha ^[5] ; Darrell J Irvine ^[7]
  1. [1] University of Oxford

     University of Oxford

     Oxford District, Reino Unido

     
  2. [2] 1 Koch Institute of Integrative Research, MIT Cambridge MA USA; 2 Ragon Institute of Harvard, MIT and MGH Cambridge MA USA
  3. [3] 3 Department of Mechanical Engineering MIT Cambridge MA USA; 9Present address: Department of Biomedical Engineering Yale University New Haven CT USA
  4. [4] 1 Koch Institute of Integrative Research, MIT Cambridge MA USA; 3 Department of Mechanical Engineering MIT Cambridge MA USA
  5. [5] 4 Division of Immunology Boston Children's Hospital Harvard Medical School Boston MA USA
  6. [6] 5 Whitehead Institute of Biomedical Research Cambridge MA USA
  7. [7] 1 Koch Institute of Integrative Research, MIT Cambridge MA USA; 2 Ragon Institute of Harvard, MIT and MGH Cambridge MA USA; 7 Department of Biological Engineering MIT Cambridge MA USA; 8 Howard Hughes Medical Institute Chevy Chase MD USA

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 39, Nº. 5, 2020
• Idioma: inglés
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  • When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact.