A LAT-Based Signaling Complex in the Immunological Synapse as Determined with Live Cell Imaging Is Less Stable in T Cells with Regulatory Capability

Autor: Elaine V. Hill, Silvia Cirillo, Simon J. Dovedi, Christoph Wülfing, Helen M Tunbridge, Yikui Li, Farnaz Fallah-Arani, Clare Thompson, Parisa Sinai, David C. Wraith, Graham J. Britton
Rok vydání: 2020
Předmět:
regulatory T cell
Immunological Synapses
Regulatory T cell
T cell
Receptors
Antigen
T-Cell

Linker for Activation of T cells
Antigen-Presenting Cells
Mice
Transgenic

Lymphocyte Activation
T-Lymphocytes
Regulatory

Article
Immunological synapse
PD-1
medicine
supramolecular signalling complex
Animals
supramolecular signaling complex
Antigen-presenting cell
lcsh:QH301-705.5
Adaptor Proteins
Signal Transducing

tolerance
biology
Chemistry
T-cell receptor
immunological synapse
linker for activation of T cells (LAT)
inhibitory receptors

General Medicine
Myelin basic protein
Cell biology
inhibitory receptors
medicine.anatomical_structure
lcsh:Biology (General)
CTLA-4
central supramolecular activation cluster (cSMAC)
biology.protein
central supramolecular activation cluster (cSMAC)
supramolecular signaling complex

linker for activation of T cells (LAT)
Signal Transduction
Zdroj: et al. 2021, ' A LAT-Based Signaling Complex in the Immunological Synapse as Determined with Live Cell Imaging Is Less Stable in T Cells with Regulatory Capability ', Cells, vol. 10, no. 2, 418, pp. 1-23 . https://doi.org/10.3390/cells10020418
Cells, Vol 10, Iss 418, p 418 (2021)
Cells
Volume 10
Issue 2
ISSN: 2073-4409
DOI: 10.3390/cells10020418
Popis: Peripheral immune regulation is critical for the maintenance of self-tolerance. Here we have investigated signaling processes that distinguish T cells with regulatory capability from effector T cells. The murine Tg4 T cell receptor recognizes a peptide derived from the self-antigen myelin basic protein. T cells from Tg4 T cell receptor transgenic mice can be used to generate effector T cells and three types of T cells with regulatory capability, inducible regulatory T cells, T cells tolerized by repeated in vivo antigenic peptide exposure or T cells treated with the tolerogenic drug UCB9608 (a phosphatidylinositol 4 kinase IIIβ inhibitor). We comparatively studied signaling in all of these T cells by activating them with the same antigen presenting cells presenting the same myelin basic protein peptide. Supramolecular signaling structures, as efficiently detected by large-scale live cell imaging, are critical mediators of T cell activation. The formation of a supramolecular signaling complex anchored by the adaptor protein linker for activation of T cells (LAT) was consistently terminated more rapidly in Tg4 T cells with regulatory capability. Such termination could be partially reversed by blocking the inhibitory receptors CTLA-4 and PD-1. Our work suggests that attenuation of proximal signaling may favor regulatory over effector function in T cells.
Databáze: OpenAIRE
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