Interfacial actin protrusions mechanically enhance killing by cytotoxic T cells Journal Article

   


Authors: Tamzalit, F.; Wang, M. S.; Jin, W.; Tello-Lafoz, M.; Boyko, V.; Heddleston, J. M.; Black, C. T.; Kam, L. C.; Huse, M.
Article Title: Interfacial actin protrusions mechanically enhance killing by cytotoxic T cells
Abstract: Cytotoxic T lymphocytes (CTLs) kill by forming immunological synapses with target cells and secreting toxic proteases and the pore-forming protein perforin into the intercellular space. Immunological synapses are highly dynamic structures that boost perforin activity by applying mechanical force against the target cell. Here, we used high-resolution imaging and microfabrication to investigate how CTLs exert synaptic forces and coordinate their mechanical output with perforin secretion. Using micropatterned stimulatory substrates that enable synapse growth in three dimensions, we found that perforin release occurs at the base of actin-rich protrusions that extend from central and intermediate locations within the synapse. These protrusions, which depended on the cytoskeletal regulator WASP and the Arp2/3 actin nucleation complex, were required for synaptic force exertion and efficient killing. They also mediated physical deformation of the target cell surface during CTL-target cell interactions. Our results reveal the mechanical basis of cellular cytotoxicity and highlight the functional importance of dynamic, three-dimensional architecture in immune cell-cell interfaces. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Journal Title: Science Immunology
Volume: 4
Issue: 33
ISSN: 2470-9468
Publisher: Amer Assoc Advancement Science  
Date Published: 2019-03-22
Start Page: eaav5445
Language: English
DOI: 10.1126/sciimmunol.aav5445
PUBMED: 30902904
PROVIDER: scopus
PMCID: PMC6746172
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063680715&doi=10.1126%2fsciimmunol.aav5445&partnerID=40&md5=6301b9345feb89704aa0843e6df55b12
Notes: Source: Scopus
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MSK Authors
  1. Morgan Huse
    68 Huse
  2. Vitaly P Boyko
    8 Boyko
  3. Fella Tamzalit
    7 Tamzalit
  4. Maria Tello Lafoz
    12 Tello Lafoz
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