@article {Anderson485, author = {R P Anderson and D A van Heel and J A Tye-Din and D P Jewell and A V S Hill}, title = {Antagonists and non-toxic variants of the dominant wheat gliadin T cell epitope in coeliac disease}, volume = {55}, number = {4}, pages = {485--491}, year = {2006}, doi = {10.1136/gut.2005.064550}, publisher = {BMJ Publishing Group}, abstract = {Background: Coeliac disease (CD) is due to an inappropriate T cell mediated response to specific gluten peptides. Measured by interferon γ (IFN-γ) ELISPOT, about half of the gliadin specific T cells induced with in vivo wheat gluten exposure in HLA-DQ2+ CD are specific for an α/β-gliadin peptide (p57{\textendash}73 QE65; QLQPFPQPELPYPQPQS) that includes two overlapping T cell epitopes (PFPQPELPY and PQPELPYPQ). Aim: To define minimally substituted variants of p57{\textendash}73 QE65 universally devoid of IFN-γ stimulatory capacity but capable of antagonising IFN-γ secretion from polyclonal T cells specific for p57{\textendash}73 QE65. Methods: 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{\textendash}73 QE65 for cytokine stimulatory and antagonist activity. Results: The region p60{\textendash}71 (PFPQPELPYPQP) and especially p64{\textendash}67 (PELP) was sensitive to substitution. Twelve substitutions in p64{\textendash}67 stimulated no IFN-γ ELISPOT response. Among 131 partial agonists identified, 45 produced statistically significant inhibition of IFN-γ ELISPOT responses when cocultured in fivefold excess with p57{\textendash}73 QE65 (n = 10). Four substituted variants of p57{\textendash}73 QE65 were inactive by IFN-γ ELISPOT but consistently antagonised IFN-γ ELISPOT responses to p57{\textendash}73 QE65, and also retained interleukin 10 stimulatory capacity similar to p57{\textendash}73 QE65. Conclusions: Altered peptide ligands of p57{\textendash}73 QE65, identified using polyclonal T cells from multiple HLA-DQ2+ CD donors, have properties in vitro that suggest that a single substitution to certain α/β-gliadins could abolish their capacity to stimulate IFN-γ from CD4 T cells and also have anti-inflammatory or protective effects in HLA-DQ2+ CD.}, issn = {0017-5749}, URL = {https://gut.bmj.com/content/55/4/485}, eprint = {https://gut.bmj.com/content/55/4/485.full.pdf}, journal = {Gut} }