Characterization of cereal toxicity for celiac disease patients based on protein homology in grains

L. Willemijn Vader, Dariusz T. Stepniak, Evelien M. Bunnik, Yvonne M.C. Kooy, Willeke De Haan, Jan Wouter Drijfhout, Peter A. Van Veelen, Frits Koning

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

Background & Aims: Celiac disease is caused by T-cell responses to wheat gluten-derived peptides. The presence of such peptides in other widely consumed grains, however, has hardly been studied. Methods: We have performed homology searches to identify regions with sequence similarity to T-cell stimulatory gluten peptides in the available gluten sequences: the hordeins of barley, secalins of rye, and avenins of oats. The identified peptides were tested for T-cell stimulatory properties. Results: With 1 exception, no identical matches with T-cell stimulatory gluten peptides were found in the other grains. However, less stringent searches identified 11 homologous sequences in hordeins, secalins, and avenins located in regions similar to those in the original gluten proteins. Seven of these 11 peptides were recognized by gluten-specific T-cell lines and/or clones from patients with celiac disease. Comparison of T-cell stimulatory sequences with homologous but non-T-cell stimulatory sequences indicated key amino acids that on substitution either completely or partially abrogated the T-cell stimulatory activity of the gluten peptides. Finally, we show that single nucleotide substitutions in gluten genes will suffice to induce these effects. Conclusions: These results show that the disease-inducing properties of barley and rye can in part be explained by T-cell cross-reactivity against gluten-, secalin-, and hordein-derived peptides. Moreover, the results provide a first step toward a rational strategy for gluten detoxification via targeted mutagenesis at the genetic level.

Original languageEnglish (US)
Pages (from-to)1105-1113
Number of pages9
JournalGastroenterology
Volume125
Issue number4
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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