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A LAT-Based Signaling Complex in the Immunological Synapse as Determined with Live Cell Imaging is Less Stable in T Cells with Regulatory Capability
| Content Provider | MDPI |
|---|---|
| Author | Christoph, Wülfing Li, Yikui Tunbridge, Helen Britton, Graham Hill, Elaine Sinai, Parisa Cirillo, Silvia Thompson, Clare Fallah-Arani, Farnaz Dovedi, Simon Wraith, David |
| Copyright Year | 2021 |
| Description | 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 쮖08 (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. |
| Starting Page | 418 |
| e-ISSN | 20734409 |
| DOI | 10.3390/cells10020418 |
| Journal | Cells |
| Issue Number | 2 |
| Volume Number | 10 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-02-17 |
| Access Restriction | Open |
| Subject Keyword | Cells Immunology Regulatory T Cell Tolerance Immunological Synapse Central Supramolecular Activation Cluster (csmac), Supramolecular Signaling Complex Linker for Activation of T Cells (lat), Inhibitory Receptors Ctla-4 Pd-1 |
| Content Type | Text |
| Resource Type | Article |
