The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Identification and Analysis of Multivalent Proteolytically Resistant Peptides from Gluten: Implications for Celiac Sprue
Open accessAbstract
Dietary gluten proteins from wheat, rye, and barley are the primary triggers for the immuno-pathogenesis of Celiac Sprue, a widespread immune disease of the small intestine. Recent molecular and structural analyses of representative gluten proteins, most notably alpha- and gamma-gliadin proteins from wheat, have improved our understanding of these pathogenic mechanisms. In particular, based on the properties of a 33-mer peptide, generated from alpha-gliadin under physiological conditions, a link between digestive resistance and inflammatory character of gluten has been proposed. Here, we report three lines of investigation in support of this hypothesis. First, biochemical and immunological analysis of deletion mutants of alpha-2 gliadin confirmed that the DQ2 restricted T cell response to the alpha-2 gliadin are directed toward the epitopes clustered within the 33-mer. Second, proteolytic analysis of a representative gamma-gliadin led to the identification of another multivalent 26-mer peptide that was also resistant to further gastric, pancreatic and intestinal brush border degradation, and was a good substrate of human transglutaminase 2 (TG2). Analogous to the 33-mer, the synthetic 26-mer peptide displayed markedly enhanced T cell antigenicity compared to monovalent control peptides. Finally, in silico analysis of the gluten proteome led to the identification of at least 60 putative peptides that share the common characteristics of the 33-mer and the 26-mer peptides. Together, these results highlight the pivotal role of physiologically generated, proteolytically stable, TG2-reactive, multivalent peptides in the immune response to dietary gluten in Celiac Sprue patients. Prolyl endopeptidase treatment was shown to abolish the antigenicity of both the 33-mer and the 26-mer peptides, and was also predicted to have comparable effects on other proline-rich putatively immunotoxic peptides identified from other polypeptides within the gluten proteome.
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Cites
Structural Basis for Gluten Intolerance in Celiac Sprue
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Self-citationCoeliac disease: dissecting a complex inflammatory disorder
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A Direct Role for NKG2D/MICA Interaction in Villous Atrophy during Celiac Disease
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Self-citationMolecular Basis of Celiac Disease
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Mortality in patients with coeliac disease and their relatives: a cohort study
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Cited by
Celiac disease: pathogenesis of a model immunogenetic disease
Kagnoff, M. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30253 · Cited by 386
Advances in Celiac Disease and Gluten-Free Diet
Niewinski, M. M. (2008) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2008.01.011 · Cited by 280
Nutritional Keys for Intestinal Barrier Modulation
De Santis, S., Cavalcanti, E., Mastronardi, M., Jirillo, E., & Chieppa, M. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00612 · Cited by 232
Laparra, J. M., & Sanz, Y. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22459 · Cited by 131
Outcome measures in coeliac disease trials: the Tampere recommendations
Ludvigsson, J. F., Ciacci, C., Green, P. H., Kaukinen, K., Korponay-Szabo, I. R., Kurppa, K., Murray, J. A., Lundin, K. E. A., Maki, M. J., Popp, A., et al. (2018) · Gut · doi:10.1136/gutjnl-2017-314853 · Cited by 100
Metadata
- Authors
- Shan, L., Qiao, S.-W., Arentz-Hansen, H., Molberg, Ø., Gray, G. M., Sollid, L. M., & Khosla, C.
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2005-08-17
- Volume
- 4
- Issue
- 5
- Pages
- 1732-1741
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W2040866634
- Cited by
- 273
- References
- 34
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- green
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- Shan, L., Qiao, S.-W., Arentz-Hansen, H., Molberg, Ø., Gray, G. M., Sollid, L. M., & Khosla, C. (2005). Identification and Analysis of Multivalent Proteolytically Resistant Peptides from Gluten: Implications for Celiac Sprue. Journal of Proteome Research. https://doi.org/10.1021/pr050173t
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