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 |
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| 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 |
| 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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