{"doi":"10.3390/cells10020418","title":"A LAT-Based Signaling Complex in the Immunological Synapse as Determined with Live Cell Imaging Is Less Stable in T Cells with Regulatory Capability","abstract":"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.","journal":"Cells","year":2021,"id":205260,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":788201,"name":"Helen M. Tunbridge","orcid":"0000-0002-8802-5979","position":1,"is_corresponding":false},{"id":105214,"name":"Graham J. Britton","orcid":"0000-0003-4630-1223","position":2,"is_corresponding":false},{"id":788583,"name":"Elaine V. Hill","orcid":null,"position":3,"is_corresponding":false},{"id":788584,"name":"Parisa Sinai","orcid":null,"position":4,"is_corresponding":false},{"id":495820,"name":"Silvia Cirillo","orcid":"0000-0002-9039-0326","position":5,"is_corresponding":false},{"id":788585,"name":"Clare Thompson","orcid":null,"position":6,"is_corresponding":false},{"id":788586,"name":"Farnaz Fallah‐Arani","orcid":null,"position":7,"is_corresponding":false},{"id":495826,"name":"Simon J. Dovedi","orcid":"0000-0003-0486-1206","position":8,"is_corresponding":false},{"id":550698,"name":"David C. Wraith","orcid":"0000-0003-2147-5614","position":9,"is_corresponding":false},{"id":496715,"name":"Christoph Wülfing","orcid":null,"position":10,"is_corresponding":false},{"id":788200,"name":"Yikui Li","orcid":"0000-0002-6879-1238","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:51:30.197308Z","pmid":"33671236","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}