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Digestive Diseases and Sciences

, Volume 53, Issue 11, pp 2917–2924 | Cite as

Deamidation of Gliadin Peptides in Lamina Propria: Implications for Celiac Disease

  • H. SkovbjergEmail author
  • D. Anthonsen
  • E. Knudsen
  • H. Sjöström
Original Article

Abstract

Activation of small intestinal gluten-reactive CD4+ T-cells is a critical event in celiac disease. Deamidation of specific glutamine residues by tissue transglutaminase enhances the binding of T-cell activating gliadin epitopes to DQ2, increasing T-cell recognition. Our purpose was to investigate whether deamidated gliadin epitopes can be generated in the small intestinal mucosa by tissue transglutaminase and to characterize the location of the process. Intestinal explants from pig intestine and frozen biopsy slices from human and rat intestine were incubated with α-gliadin peptides containing the immunodominant motif. Monoclonal antibodies specifically recognizing the non-deamidated and/or the deamidated epitope were used for immunofluorescence studies. We conclude that endogenous tissue transglutaminase can mediate extracellular deamidation of gliadin peptides in the lamina propria. Gliadin peptides with more than one recognition site can be simultaneously cross-linked and deamidated extracellularly in the lamina propria, and might be of importance for the antibody response seen in untreated celiac disease patients.

Keywords

Celiac disease Transglutaminase Gliadin peptides Cross-linking Deamidation 

Notes

Acknowledgments

Associate professor Gert Hansen, Department of Medical Biochemistry and Genetics, University of Copenhagen, is thanked for assistance with the immunofluorescense microscopic studies. The work was supported by The Novo Nordisk Foundation. Ethics approval: The study was approved by the scientific-ethical committees for Copenhagen and Frederiksberg (KF) 01-147/04.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • H. Skovbjerg
    • 1
    • 2
    Email author
  • D. Anthonsen
    • 1
  • E. Knudsen
    • 2
  • H. Sjöström
    • 1
  1. 1.Department of Cellular and Molecular MedicineThe Panum Institute, University of CopenhagenCopenhagen NDenmark
  2. 2.Medical CentreAmager HospitalCopenhagen NDenmark

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