title: Coeliac disease: immunogenicity studies of barley hordein and rye secalin-derived peptides.
abstract: Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A ω-gliadin/C-hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T-cell lines obtained from CD small intestinal biopsies. We also sought to investigate the potential cross-reactivity of wheat gluten-sensitive T-cell lines with peptic-tryptic digested barley hordein (PTH) and rye secalin (PTS). Synthesised candidate peptides were deamidated with tissue transglutaminase (tTG). Gluten-sensitive T-cell lines were generated by culturing small intestinal biopsies from CD patients with peptic-tryptic gluten (PTG), PTH or PTS, along with autologous PBMCs for antigen presentation. The stimulation indices were determined by measuring the relative cellular proliferation via incorporation of3H-thymidine. The majority of T-cell lines reacted to the peptides studied. There was also cross-reactivity between wheat gluten-sensitive T-cell lines and the hordein, gliadin and secalin peptides. PTH, PTS, barley hordein and rye secalin-derived CD antigen-sensitive T-cell lines showed positive stimulation with PTG. ω-gliadin/C-hordein peptide and rye-derived peptide are immunogenic to gluten-sensitive T-cell lines and potentially present in wheat, rye and barley. Additional CD toxic peptides may be shared.
authors.affiliation: Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia (IIUM), Kuantan, Malaysia.
authors.forename: Widya A
authors.initials: WA
authors.lastname: Wahab
authors.affiliation: Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK.
authors.forename: Tanja
authors.initials: T
authors.lastname: Šuligoj
authors.affiliation: Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Ellis
authors.affiliation: Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Côrtez-Real
authors.affiliation: Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK. paul.ciclitira@kcl.ac.uk.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Ciclitira
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D001706:Biopsy; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D005983:Glutens / Q000276:immunology*; D001467:Hordeum / Q000276:immunology*; D006801:Humans; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D012434:Secale / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D005983:Glutens
keywords: antigen presentation; coeliac disease; gluten; small intestinal T-cell lines