{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:39:47Z","timestamp":1772156387007,"version":"3.50.1"},"posted":{"date-parts":[[2024,1,12]]},"group-title":"Immunology","reference-count":96,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  During thymic development, most \u03b3\u03b4 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 \u03b3\u03b4 T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM-SAP signaling pathway regulates the development and function of multiple innate-like \u03b3\u03b4 T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent \u03b3\u03b4 TCR repertoire. SAP deficiency resulted in both a significant loss of an immature\n                  <jats:italic>Gzma<\/jats:italic>\n                  <jats:sup>+<\/jats:sup>\n                  <jats:italic>\n                    Blk\n                    <jats:sup>+<\/jats:sup>\n                    Etv5\n                    <jats:sup>+<\/jats:sup>\n                    Tox2\n                    <jats:sup>+<\/jats:sup>\n                  <\/jats:italic>\n                  \u03b3\u03b4T17 precursor population, and a significant increase in\n                  <jats:italic>\n                    Cd4\n                    <jats:sup>+<\/jats:sup>\n                    Cd8\n                    <jats:sup>+<\/jats:sup>\n                    Rorc\n                    <jats:sup>+<\/jats:sup>\n                    Ptcra\n                    <jats:sup>+<\/jats:sup>\n                    Rag1\n                    <jats:sup>+<\/jats:sup>\n                  <\/jats:italic>\n                  thymic \u03b3\u03b4 T cells. SAP-dependent diversion of embryonic day 17 thymic \u03b3\u03b4 T cell clonotypes into the \u03b1\u03b2 T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered \u03b3\u03b4 TCR repertoire in the periphery. Finally, we identify TRGV4\/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent V\u03b34 \u03b3\u03b4T1 subset. Together, the data suggest that SAP-dependent \u03b3\u03b4\/\u03b1\u03b2 T cell lineage commitment regulates \u03b3\u03b4 T cell developmental programming and shapes the \u03b3\u03b4 TCR repertoire.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"575073v3_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2024.01.10.575073","type":"posted-content","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T18:40:17Z","timestamp":1705084817000},"source":"Crossref","is-referenced-by-count":0,"title":["SLAM\/SAP signaling regulates discrete \u03b3\u03b4 T cell developmental checkpoints and shapes the innate-like \u03b3\u03b4 TCR repertoire"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-6927","authenticated-orcid":false,"given":"Somen K","family":"Mistri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brianna M.","family":"Hilton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine J.","family":"Horrigan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6827-1933","authenticated-orcid":false,"given":"Emma S.","family":"Andretta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remi","family":"Savard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9380-4873","authenticated-orcid":false,"given":"Oliver","family":"Dienz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth J","family":"Hampel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana L.","family":"Gerrard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua T.","family":"Rose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikoletta","family":"Sidiropoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2541-3851","authenticated-orcid":false,"given":"Devdoot","family":"Majumdar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-9148","authenticated-orcid":false,"given":"Jonathan E.","family":"Boyson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024070403050861000_2024.01.10.575073v3.1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.5.2413"},{"key":"2024070403050861000_2024.01.10.575073v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.06.003"},{"key":"2024070403050861000_2024.01.10.575073v3.3","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1717"},{"key":"2024070403050861000_2024.01.10.575073v3.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.071"},{"key":"2024070403050861000_2024.01.10.575073v3.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.11.004"},{"key":"2024070403050861000_2024.01.10.575073v3.6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903767"},{"key":"2024070403050861000_2024.01.10.575073v3.7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030584"},{"key":"2024070403050861000_2024.01.10.575073v3.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063916"},{"key":"2024070403050861000_2024.01.10.575073v3.9","doi-asserted-by":"publisher","DOI":"10.1038\/nature14282"},{"key":"2024070403050861000_2024.01.10.575073v3.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.03.013"},{"key":"2024070403050861000_2024.01.10.575073v3.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1403424111"},{"key":"2024070403050861000_2024.01.10.575073v3.12","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200940157"},{"key":"2024070403050861000_2024.01.10.575073v3.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.04.018"},{"key":"2024070403050861000_2024.01.10.575073v3.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.04.022"},{"key":"2024070403050861000_2024.01.10.575073v3.15","doi-asserted-by":"crossref","unstructured":"Munoz-Ruiz M , et al. 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