{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T11:02:06Z","timestamp":1765623726969,"version":"3.48.0"},"reference-count":23,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Coeliac disease (CD) is due to an inappropriate T cell mediated response to specific gluten peptides. Measured by interferon \u03b3 (IFN-\u03b3) ELISPOT, about half of the gliadin specific T cells induced with in vivo wheat gluten exposure in HLA-DQ2+ CD are specific for an \u03b1\/\u03b2-gliadin peptide (p57\u201373 QE65; QLQPFPQPELPYPQPQS) that includes two overlapping T cell epitopes (PFPQPELPY and PQPELPYPQ).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aim:<\/jats:bold>\n                    To define minimally substituted variants of p57\u201373 QE65 universally devoid of IFN-\u03b3 stimulatory capacity but capable of antagonising IFN-\u03b3 secretion from polyclonal T cells specific for p57\u201373 QE65.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Peripheral blood mononuclear cells collected from 75 HLA-DQ2+ CD patients after in vivo gluten challenge were used in overnight ELISPOT assays to screen 218 single or double substituted variants of p57\u201373 QE65 for cytokine stimulatory and antagonist activity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The region p60\u201371 (PFPQPELPYPQP) and especially p64\u201367 (PELP) was sensitive to substitution. Twelve substitutions in p64\u201367 stimulated no IFN-\u03b3 ELISPOT response. Among 131 partial agonists identified, 45 produced statistically significant inhibition of IFN-\u03b3 ELISPOT responses when cocultured in fivefold excess with p57\u201373 QE65 (n\u200a=\u200a10). Four substituted variants of p57\u201373 QE65 were inactive by IFN-\u03b3 ELISPOT but consistently antagonised IFN-\u03b3 ELISPOT responses to p57\u201373 QE65, and also retained interleukin 10 stimulatory capacity similar to p57\u201373 QE65.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Altered peptide ligands of p57\u201373 QE65, identified using polyclonal T cells from multiple HLA-DQ2+ CD donors, have properties in vitro that suggest that a single substitution to certain \u03b1\/\u03b2-gliadins could abolish their capacity to stimulate IFN-\u03b3 from CD4 T cells and also have anti-inflammatory or protective effects in HLA-DQ2+ CD.\n                  <\/jats:p>","DOI":"10.1136\/gut.2005.064550","type":"journal-article","created":{"date-parts":[[2005,11,18]],"date-time":"2005-11-18T20:23:56Z","timestamp":1132345436000},"page":"485-491","source":"Crossref","is-referenced-by-count":49,"title":["Antagonists and non-toxic variants of the dominant wheat gliadin T cell epitope in coeliac disease"],"prefix":"10.1136","volume":"55","author":[{"given":"R P","family":"Anderson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D A","family":"van Heel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A","family":"Tye-Din","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D P","family":"Jewell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A V S","family":"Hill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2005,11,18]]},"reference":[{"key":"2025121303010074000_55.4.485.1","doi-asserted-by":"publisher","DOI":"10.1016\/0950-3528(95)90027-6"},{"key":"2025121303010074000_55.4.485.2","doi-asserted-by":"publisher","DOI":"10.1038\/369403a0"},{"key":"2025121303010074000_55.4.485.3","doi-asserted-by":"publisher","DOI":"10.1038\/369407a0"},{"key":"2025121303010074000_55.4.485.4","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.4049\/jimmunol.153.7.3326","volume":"153","year":"1994","journal-title":"J Immunol"},{"key":"2025121303010074000_55.4.485.5","doi-asserted-by":"publisher","DOI":"10.1038\/80516"},{"key":"2025121303010074000_55.4.485.6","doi-asserted-by":"publisher","DOI":"10.1038\/80525"},{"key":"2025121303010074000_55.4.485.7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.7.1033"},{"key":"2025121303010074000_55.4.485.8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.6.3893"},{"key":"2025121303010074000_55.4.485.9","doi-asserted-by":"publisher","DOI":"10.1038\/73200"},{"key":"2025121303010074000_55.4.485.10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.4.603"},{"key":"2025121303010074000_55.4.485.11","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.35381"},{"key":"2025121303010074000_55.4.485.12","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.33606"},{"key":"2025121303010074000_55.4.485.13","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.059998"},{"key":"2025121303010074000_55.4.485.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1995.tb03127.x"},{"key":"2025121303010074000_55.4.485.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1993.tb01991.x"},{"key":"2025121303010074000_55.4.485.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1997.tb02936.x"},{"key":"2025121303010074000_55.4.485.17","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80064-3"},{"key":"2025121303010074000_55.4.485.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306885101"},{"key":"2025121303010074000_55.4.485.19","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.1.187"},{"key":"2025121303010074000_55.4.485.20","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830261132"},{"key":"2025121303010074000_55.4.485.21","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.12.1698"},{"key":"2025121303010074000_55.4.485.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)01204-6"},{"key":"2025121303010074000_55.4.485.23","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20012028"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.2005.064550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T11:01:10Z","timestamp":1765623670000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.2005.064550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,18]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2006,3,10]]},"published-print":{"date-parts":[[2006,4]]}},"alternative-id":["10.1136\/gut.2005.064550"],"URL":"https:\/\/doi.org\/10.1136\/gut.2005.064550","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"subject":[],"published":{"date-parts":[[2005,11,18]]}}}