Natural variants of α-gliadin peptides within wheat proteins with reduced toxicity in coeliac disease

Nika Japelj, Tanja Suligoj, Wei Zhang, Beatriz Côrte-Real, Joachim Messing, Paul J. Ciclitira

Research output: Contribution to journalArticlepeer-review


The only generally accepted treatment of coeliac disease (CD) is a lifelong gluten-free diet. Wheat gluten proteins include gliadins, low and high molecular weight glutenins. However, we have found significant structural variations within these protein families among different cultivars. To determine which structural motifs might be less toxic than others, we assessed five variants of α-gliadin immunodominant CD-toxic peptides synthesised as 16mers in CD T cell stimulation assays with gluten-sensitive T cell lines generated from duodenal biopsies from CD-affected individuals. The peptides harboured the overlapping T cell epitopes DQ 2.5-glia-α-2 and naturally occurring variants that differed in certain amino acids (AA). The results revealed that introduction of two selected AA substitutions in α-gliadin peptides reduced immunogenicity. A peptide with three AA substitutions involving two glutamic acids (E) and one glutamine residue (G) revealed the peptide was negative in 5:5 samples. We used CD small-intestinal organ culture to assess CD toxicity that revealed two peptides with selected substitution of both glutamic acid (E) and proline (P) residues abrogated evidence of CD toxicity.

Original languageEnglish (US)
Pages (from-to)1382-1389
Number of pages8
JournalBritish Journal of Nutrition
Issue number12
StatePublished - Jun 28 2020

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


  • Coeliac disease
  • Duodenal biopsy organ culture
  • Gliadin
  • Gluten-free diet
  • Gluten-sensitive T cells
  • Low and high molecular weight glutenins

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