Research ArticlesCeliac Disease

Comprehensive, Quantitative Mapping of T Cell Epitopes in Gluten in Celiac Disease

Science Translational Medicine  21 Jul 2010:
Vol. 2, Issue 41, pp. 41ra51
DOI: 10.1126/scitranslmed.3001012

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Taming of the Sprue

Gluten, a complex protein in wheat, barley, and rye, forms the elastic network responsible for the airy texture of bread. But gluten can also trigger a prevalent inflammatory disorder—celiac disease (sprue)—which afflicts sufferers with problems such as gastrointestinal upset, fatigue, and anemia, and confers increased risks of osteoporosis, autoimmune disease, and cancer. The current therapy consists of strict lifelong avoidance of all foods containing gluten. The development of alternatives has been hampered by the inability to fully characterize the immune response to the toxic peptides within these grains. Several immunotoxic peptides from wheat have been implicated, but it has remained unclear how they contribute to the overall immune response in celiac disease, or whether other potentially toxic peptides from barley and rye exist.

Tye-Din and colleagues have now comprehensively assessed the more than 16,000 potentially toxic peptides contained within wheat, barley, and rye, and identified which ones stimulate T cells from celiac disease patients. By feeding doses of wheat, barley, or rye to more than 200 people with celiac disease, the authors were able to examine the induced T cells appearing in the bloodstream several days afterward. These T cells were then tested for recognition of peptides from large libraries encompassing every possible toxic peptide from wheat, barley, and rye.

Surprisingly, they found that just three highly active peptides were responsible for most of the immune response seen in patients with celiac disease after eating any of the toxic grains. Although the range of highly stimulatory or dominant peptides was very consistent between individuals, it was dependent on which grain was consumed. A previously described peptide from wheat α-gliadin was dominant only after wheat ingestion; another distinct peptide was dominant after wheat, barley, or rye ingestion. Of most interest was the fact that a combination of these peptides, plus another from barley, could elicit 90% of the response induced by the full complement of wheat, barley, and rye proteins.

Because the authors assessed every possible toxic peptide from wheat, as well as barley and rye, they can be confident that their data paint a comprehensive picture of the immune response in celiac disease. This is important because alternative therapies to the complex, costly, and inconvenient gluten-free diet are likely to require a detailed molecular understanding of the peptides driving the immune response in celiac disease. Multiple doses of peptides corresponding to immunodominant T cell epitopes are effective in treating a mouse version of celiac disease, and the discovery that a small number of peptides can elicit the disease in patients suggests that a similar approach may be successful in humans as well.


  • * These authors contributed equally to this work.

  • Present address: Department of Medical Statistics, University Medicine Goettingen, 37099 Goettingen, Germany.

  • Present address: St. Vincent’s Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.

  • Citation: J. A. Tye-Din, J. A. Stewart, J. A. Dromey, T. Beissbarth, D. A. van Heel, A. Tatham, K. Henderson, S. I. Mannering, C. Gianfrani, D. P. Jewell, A. V. S. Hill, J. McCluskey, J. Rossjohn, R. P. Anderson, Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease.Sci. Transl. Med. 2, 41ra51 (2010).