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This B\u2010cell\/T\u2010cell crosstalk is facilitated by involvement of TG2:gluten peptide complexes that act principally in the form of enzyme\u2010substrate intermediates. Here, we have addressed how gluten peptide affinity and complex stability in the presence of secondary substrates affect the uptake of TG2:gluten peptide complexes by TG2\u2010specific B cells and the activation of gluten\u2010specific T cells. We studied affinity of various gluten peptides for TG2 by biochemical assay, and monitored uptake of gluten peptides by TG2\u2010specific B cells by flow cytometry. Crosstalk between TG2\u2010specific B cells and gluten\u2010specific T cells was assayed with transfectants expressing antigen receptors derived from CeD patients. We found that gluten peptides with high TG2 affinity showed better uptake by TG2\u2010specific B cells. Uptake by B cells, and subsequent activation of T cells, was negatively affected by polyamines acting as secondary TG2 substrates. These results show that affinity between gluten peptide and TG2 governs the selection of T\u2010cell epitopes via enhanced uptake of TG2:gluten complexes by TG2\u2010specific B cells, and that exogenous polyamines can influence the CeD immune responses by disrupting TG2:gluten complexes.<\/jats:p>","DOI":"10.1002\/eji.202249862","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T04:14:31Z","timestamp":1655525671000},"page":"1474-1481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transglutaminase 2 affinity and enzyme\u2010substrate intermediate stability as determining factors for T\u2010cell responses to gluten peptides in celiac disease"],"prefix":"10.1002","volume":"52","author":[{"given":"Sunniva F.","family":"Amundsen","sequence":"first","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorunn","family":"Stamnaes","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie Fleur","family":"du Pr\u00e9","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"Department Immunology Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"Department Immunology Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601693"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2015.11.001"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)62626-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2014.06.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20012028"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204521200"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014056"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.41.6.851"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310198200"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.04.018"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/314537a0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3037"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-008-0126-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi011715x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050327"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00926881"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst024226s"},{"key":"e_1_2_9_19_1","first-page":"S20","article-title":"Fasting and post\u2010prandial polyamine concentrations in the human small bowel","volume":"35","author":"Sawada Y.","year":"1994","journal-title":"Gut"},{"key":"e_1_2_9_20_1","first-page":"G576","article-title":"Gastrointestinal luminal polyamines: cellular accumulation and enterohepatic circulation","volume":"258","author":"Osborne D. 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