Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells
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 polymerizat...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Royal Society of Chemistry
2015
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| _version_ | 1826261777234526208 |
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| author | Tabdanov, E Gondarenko, S Kumari, S Liapis, A Dustin, M Sheetz, M Kam, L Iskratsch, T |
| author_facet | Tabdanov, E Gondarenko, S Kumari, S Liapis, A Dustin, M Sheetz, M Kam, L Iskratsch, T |
| author_sort | Tabdanov, E |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:26:01Z |
| format | Journal article |
| id | oxford-uuid:1bb827a7-524a-4826-b3c9-f7a51d26cbd1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:26:01Z |
| publishDate | 2015 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | oxford-uuid:1bb827a7-524a-4826-b3c9-f7a51d26cbd12022-03-26T11:02:04ZMicropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1bb827a7-524a-4826-b3c9-f7a51d26cbd1EnglishSymplectic Elements at OxfordRoyal Society of Chemistry2015Tabdanov, EGondarenko, SKumari, SLiapis, ADustin, MSheetz, MKam, LIskratsch, TThe 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. |
| spellingShingle | Tabdanov, E Gondarenko, S Kumari, S Liapis, A Dustin, M Sheetz, M Kam, L Iskratsch, T Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells |
| title | Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells |
| title_full | Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells |
| title_fullStr | Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells |
| title_full_unstemmed | Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells |
| title_short | Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells |
| title_sort | micropatterning of tcr and lfa 1 ligands reveals complementary effects on cytoskeleton mechanics in t cells |
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