{"doi":"10.7554/elife.97229.3","title":"SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire","abstract":"During thymic development, most γδ T cells acquire innate-like characteristics that are critical for their function in tumor surveillance, infectious disease, and tissue repair. The mechanisms, however, that regulate γδ T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM/SAP signaling pathway regulates the development and function of multiple innate-like γδ T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent γδ TCR repertoire in mice. SAP deficiency resulted in both a significant loss of an immature Gzma + Blk + Etv5 + Tox2 + γδT17 precursor population and a significant increase in Cd4 + Cd8 + Rorc + Ptcra + Rag1 + thymic γδ T cells. SAP-dependent diversion of embryonic day 17 thymic γδ T cell clonotypes into the αβ T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered γδ TCR repertoire in the periphery. Finally, we identify TRGV4/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent Vγ4 γδT1 subset. Together, the data support a model in which SAP-dependent γδ/αβ T cell lineage commitment regulates γδ T cell developmental programming and shapes the γδ TCR repertoire.","journal":"eLife","year":2024,"id":452457,"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":0.953,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1274668,"name":"Brianna M Hilton","orcid":null,"position":1,"is_corresponding":false},{"id":1274669,"name":"Katherine J. Horrigan","orcid":null,"position":2,"is_corresponding":false},{"id":1212158,"name":"Emma S. Andretta","orcid":"0009-0006-6827-1933","position":3,"is_corresponding":false},{"id":1274670,"name":"Rémi Savard","orcid":null,"position":4,"is_corresponding":false},{"id":509763,"name":"Oliver Dienz","orcid":"0000-0001-9380-4873","position":5,"is_corresponding":false},{"id":1274671,"name":"Kenneth J Hampel","orcid":null,"position":6,"is_corresponding":false},{"id":172380,"name":"Diana L. Gerrard","orcid":null,"position":7,"is_corresponding":false},{"id":375026,"name":"Joshua T. Rose","orcid":null,"position":8,"is_corresponding":false},{"id":1274672,"name":"Nikoletta Sidiropoulos","orcid":null,"position":9,"is_corresponding":false},{"id":812689,"name":"Dev Majumdar","orcid":null,"position":10,"is_corresponding":false},{"id":356384,"name":"Jonathan E. Boyson","orcid":"0000-0003-2673-9148","position":11,"is_corresponding":false},{"id":509765,"name":"Somen K Mistri","orcid":"0000-0002-2139-6927","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-19T02:02:50.407779Z","pmid":null,"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":[]}