Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion
Supramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen-presenting cells. We have determined that it is compose...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/45789 |
| _version_ | 1811201682270322688 |
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| author | Danielle J Clark Laura E McMillan Sin Lih Tan Gaia Bellomo Clementine Massoue Harry Thompson Lidiya Mykhaylechko Dominic Alibhai Xiongtao Ruan Kentner L Singleton Minna Du Alan Hedges Pamela L Schwartzberg Paul Verkade Robert F Murphy Christoph Wülfing |
| author_facet | Danielle J Clark Laura E McMillan Sin Lih Tan Gaia Bellomo Clementine Massoue Harry Thompson Lidiya Mykhaylechko Dominic Alibhai Xiongtao Ruan Kentner L Singleton Minna Du Alan Hedges Pamela L Schwartzberg Paul Verkade Robert F Murphy Christoph Wülfing |
| author_sort | Danielle J Clark |
| collection | DOAJ |
| description | Supramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen-presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0.5 µm3 and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates. |
| first_indexed | 2024-04-12T02:25:36Z |
| format | Article |
| id | doaj.art-6c4f2dbdb6a24ac88d4cbc5f40b47ea3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:25:36Z |
| publishDate | 2019-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6c4f2dbdb6a24ac88d4cbc5f40b47ea32022-12-22T03:52:00ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.45789Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretionDanielle J Clark0Laura E McMillan1Sin Lih Tan2Gaia Bellomo3Clementine Massoue4Harry Thompson5Lidiya Mykhaylechko6Dominic Alibhai7Xiongtao Ruan8Kentner L Singleton9Minna Du10Alan Hedges11Pamela L Schwartzberg12Paul Verkade13Robert F Murphy14https://orcid.org/0000-0003-0358-901XChristoph Wülfing15https://orcid.org/0000-0002-6156-9861School of Cellular and Molecular Medicine, University of Bristol, Bristol, United KingdomSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United KingdomSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United KingdomSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United KingdomSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United KingdomSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United KingdomSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United KingdomSchool of Biochemistry, University of Bristol, Bristol, United KingdomComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United StatesDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, United StatesSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United KingdomGenetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, United StatesSchool of Biochemistry, University of Bristol, Bristol, United KingdomComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States; Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, United States; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, United States; Department of Machine Learning, Carnegie Mellon University, Pittsburgh, United States; Freiburg Institute for Advanced Studies, Albert Ludwig University of Freiburg, Freiburg, Germany; Faculty of Biology, Albert Ludwig University of Freiburg, Freiburg, GermanySchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United StatesSupramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen-presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0.5 µm3 and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates.https://elifesciences.org/articles/45789T lymphocytessupramolecular protein complexsignal transductionimaging |
| spellingShingle | Danielle J Clark Laura E McMillan Sin Lih Tan Gaia Bellomo Clementine Massoue Harry Thompson Lidiya Mykhaylechko Dominic Alibhai Xiongtao Ruan Kentner L Singleton Minna Du Alan Hedges Pamela L Schwartzberg Paul Verkade Robert F Murphy Christoph Wülfing Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion eLife T lymphocytes supramolecular protein complex signal transduction imaging |
| title | Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion |
| title_full | Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion |
| title_fullStr | Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion |
| title_full_unstemmed | Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion |
| title_short | Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion |
| title_sort | transient protein accumulation at the center of the t cell antigen presenting cell interface drives efficient il 2 secretion |
| topic | T lymphocytes supramolecular protein complex signal transduction imaging |
| url | https://elifesciences.org/articles/45789 |
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