{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:04:26Z","timestamp":1783397066806,"version":"3.54.6"},"reference-count":35,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Council of Italy (CNR) project Nutrizione, Alimentazione &amp; Invecchiamento Attivo (NUTR-AGE, FOE-2019, DSB.AD004.271)","award":["DSB.AD004.271)"],"award-info":[{"award-number":["DSB.AD004.271)"]}]},{"name":"METROFOODPP European Union\u2019s Horizon 2020 Research and Innovation Program","award":["No. 871083"],"award-info":[{"award-number":["No. 871083"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Enzymatic transamidation of gliadins by microbial transglutaminase (mTG) inhibits interferon-\u03b3 (IFN-\u03b3) secretion by intestinal T cell lines in patients with celiac disease (CD). To gain insight into the cellular mechanisms underlying the down-regulatory effects of transamidation, we tested a single recombinant \u03b1-gliadin (r-gliadin) harbouring two immunodominant peptides, p13 (aa. 120\u2013139) and p23 (aa. 220\u2013239), in HLA-DQ8 transgenic mice, a model of gluten sensitivity. Mice were intranasally immunised with r-gliadin or r-gliadin transamidated by mTG (K-r-gliadin) along with cholera toxin, and the response of mesenteric lymph node cells was analysed by cytokine multiplex assay. An in vitro challenge with r-gliadin was characterised by secretion of specific cytokines featuring both innate immunity and the Th1\/Th2\/Th17 pattern of the adaptive response. Notably, transamidation specifically down-regulated the Th1 response. Structural studies performed on K-r-gliadin confirmed that specific glutamine residues in p13 and p23, previously found to be deamidated by tissue transglutaminase, were also transamidated by mTG. In silico analysis, simulating p13 and p23 peptide binding to HLA-DQ8 showed that these glutamines, in the form of glutamate, could interact by means of salt bridges with peculiar amino acids of the alpha chain of HLA-DQ8, suggesting that their transamidation may influence the HLA-restricted recognition of these peptides. Thus, the structural findings provided a rationale to explain the down-regulation of the r-gliadin-specific Th1 response following transamidation.<\/jats:p>","DOI":"10.3390\/ijms22137019","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"7019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Transamidation Down-Regulates Intestinal Immunity of Recombinant \u03b1-Gliadin in HLA-DQ8 Transgenic Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Stefano","family":"Rossi","sequence":"first","affiliation":[{"name":"Immunobiology Unit, CNR, Institute of Food Sciences, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-1913","authenticated-orcid":false,"given":"Deborah","family":"Giordano","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biology Unit, CNR, Institute of Food Sciences, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1542-0027","authenticated-orcid":false,"given":"Maria Fiorella","family":"Mazzeo","sequence":"additional","affiliation":[{"name":"Proteomics and Biomolecular Mass Spectrometry Center, CNR, Institute of Food Sciences, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Maurano","sequence":"additional","affiliation":[{"name":"Immunobiology Unit, CNR, Institute of Food Sciences, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diomira","family":"Luongo","sequence":"additional","affiliation":[{"name":"Immunobiology Unit, CNR, Institute of Food Sciences, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-4912","authenticated-orcid":false,"given":"Angelo","family":"Facchiano","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biology Unit, CNR, Institute of Food Sciences, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Anna","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Proteomics and Biomolecular Mass Spectrometry Center, CNR, Institute of Food Sciences, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8631-1683","authenticated-orcid":false,"given":"Mauro","family":"Rossi","sequence":"additional","affiliation":[{"name":"Immunobiology Unit, CNR, Institute of Food Sciences, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nsmb.2826","article-title":"How T cells taste gluten in celiac disease","volume":"21","author":"Jabri","year":"2014","journal-title":"Nat. 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