Projects per year
Abstract
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.
Original language | English |
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Article number | e45789 |
Number of pages | 29 |
Journal | eLife |
Volume | 8 |
DOIs | |
Publication status | Published - 30 Oct 2019 |
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Dive into the research topics of 'Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion'. Together they form a unique fingerprint.Projects
- 1 Finished
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Causal modeling of T cell signaling in time and space - Proposal no. 7632552
Wuelfing, C. (Principal Investigator)
1/10/18 → 30/09/19
Project: Research
Profiles
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Professor Christoph Wuelfing
- School of Cellular and Molecular Medicine - Professor of Immunology
- Infection and Immunity
- Cancer
Person: Academic , Member