{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:13:21Z","timestamp":1774671201014,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":1944,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Lack of understanding of the nature and physiological regulation of \u03b3\u03b4 T cell ligands has considerably hampered full understanding of the function of these cells. We developed an unbiased approach to identify human \u03b3\u03b4 T cells ligands by the production of a soluble TCR-\u03b3\u03b4 (sTCR-\u03b3\u03b4) tetramer from a synovial V\u03b41 \u03b3\u03b4 T cell clone from a Lyme arthritis patient. The sTCR-\u03b3\u03b4 was used in flow cytometry to initially define the spectrum of ligand expression by both human tumor cell lines and certain human primary cells. Analysis of diverse tumor cell lines revealed high ligand expression on several of epithelial or fibroblast origin, whereas those of hematopoietic origin were largely devoid of ligand. This allowed a bioinformatics-based identification of candidate ligands using RNAseq data from each tumor line. We further observed that whereas fresh monocytes and T cells expressed low to negligible levels of TCR-\u03b3\u03b4 ligands, activation of these cells resulted in upregulation of surface ligand expression. Ligand upregulation on monocytes was partly dependent upon IL-1\u03b2. The sTCR-\u03b3\u03b4 tetramer was then used to bind candidate ligands from lysates of activated monocytes and analyzed by mass spectrometry. Surface TCR-\u03b3\u03b4 ligand was eliminated by treatment with trypsin or removal of glycosaminoglycans, and also suppressed by inhibition of endoplasmic reticulum\u2013Golgi transport. Of particular interest was that inhibition of glycolysis also blocked TCR-\u03b3\u03b4 ligand expression. These findings demonstrate the spectrum of ligand(s) expression for human synovial V\u03b41 \u03b3\u03b4 T cells as well as the physiology that regulates their expression.<\/jats:p>","DOI":"10.4049\/jimmunol.1900451","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T18:35:23Z","timestamp":1569263723000},"page":"2369-2376","source":"Crossref","is-referenced-by-count":6,"title":["Detection of Cell Surface Ligands for Human Synovial \u03b3\u03b4 T Cells"],"prefix":"10.1093","volume":"203","author":[{"given":"Cheryl","family":"Collins","sequence":"first","affiliation":[{"name":"Vermont Center for Immunology and Infectious Diseases, Department of Medicine, Larner College of Medicine, The University of Vermont , Burlington, VT 05405"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Lui","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, John Radcliffe Hospital , Headington, Oxford OX3 9DS ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Mafalda","family":"Santos","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, John Radcliffe Hospital , Headington, Oxford OX3 9DS ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan A","family":"Ballif","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Arts and Sciences, The University of Vermont , Burlington, VT 05405"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6982-2078","authenticated-orcid":false,"given":"Anisha Mahalya","family":"Gogerly-Moragoda","sequence":"additional","affiliation":[{"name":"Vermont Center for Immunology and Infectious Diseases, Department of Medicine, Larner College of Medicine, The University of Vermont , Burlington, VT 05405"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-6834","authenticated-orcid":false,"given":"Heather","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, John Radcliffe Hospital , Headington, Oxford OX3 9DS ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuberan","family":"Balagurunathan","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Utah , Salt Lake City, UT 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0598-2181","authenticated-orcid":false,"given":"Sumana","family":"Sharma","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute , Cambridge CB10 1SA ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin J","family":"Wright","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute , Cambridge CB10 1SA ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Davis","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, John Radcliffe Hospital , Headington, Oxford OX3 9DS ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph C","family":"Budd","sequence":"additional","affiliation":[{"name":"Vermont Center for Immunology and Infectious Diseases, Department of Medicine, Larner College of Medicine, The University of Vermont , Burlington, VT 05405"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,11,1]]},"reference":[{"key":"2025030417543764100_r1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0065-2776(08)60400-9","article-title":"Immunoregulatory functions of gamma delta T cells","volume":"71","author":"Born","year":"1999","journal-title":"Adv. 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