The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Specificity of Tissue Transglutaminase Explains Cereal Toxicity in Celiac Disease
Open accessAbstract
Celiac disease is caused by a selective lack of T cell tolerance for gluten. It is known that the enzyme tissue transglutaminase (tTG) is involved in the generation of T cell stimulatory gluten peptides through deamidation of glutamine, the most abundant amino acid in gluten. Only particular glutamine residues, however, are modified by tTG. Here we provide evidence that the spacing between glutamine and proline, the second most abundant amino acid in gluten, plays an essential role in the specificity of deamidation. On the basis of this, algorithms were designed and used to successfully predict novel T cell stimulatory peptides in gluten. Strikingly, these algorithms identified many similar peptides in the gluten-like hordeins from barley and secalins from rye but not in the avenins from oats. The avenins contain significantly lower percentages of proline residues, which offers a likely explanation for the lack of toxicity of oats. Thus, the unique amino acid composition of gluten and related proteins in barley and rye favors the generation of toxic T cell stimulatory gluten peptides by tTG. This provides a rationale for the observation that celiac disease patients are intolerant to these cereal proteins but not to other common food proteins.
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Cites
Identification of tissue transglutaminase as the autoantigen of celiac disease
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The Oslo definitions for coeliac disease and related terms
Ludvigsson, J. F., Leffler, D. A., Bai, J. C., Biagi, F., Fasano, A., Green, P. H. R., Hadjivassiliou, M., Kaukinen, K., Kelly, C. P., Leonard, J. N., et al. (2013) · Gut · doi:10.1136/gutjnl-2011-301346 · Cited by 1,721
Coeliac disease: dissecting a complex inflammatory disorder
Sollid, L. M. (2002) · Nature Reviews Immunology · doi:10.1038/nri885 · Cited by 964
Celiac disease: pathogenesis of a model immunogenetic disease
Kagnoff, M. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30253 · Cited by 386
Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder
Dunne, M. R., Byrne, G., Chirdo, F. G., & Feighery, C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01374 · Cited by 85
Metadata
- Authors
- Vader, L. W., de Ru, A., van der Wal, Y., Kooy, Y. M. C., Benckhuijsen, W., Mearin, M. L., Drijfhout, J. W., van Veelen, P., & Koning, F.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2002-03-04
- Volume
- 195
- Issue
- 5
- Pages
- 643-649
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2119520032
- Cited by
- 357
- References
- 16
- FWCI
- 19.31
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Vader, L. W., de Ru, A., van der Wal, Y., Kooy, Y. M. C., Benckhuijsen, W., Mearin, M. L., Drijfhout, J. W., van Veelen, P., & Koning, F. (2002). Specificity of Tissue Transglutaminase Explains Cereal Toxicity in Celiac Disease. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20012028
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