Skip to main content

On the Role of Dipeptidyl Peptidase IV in the Digestion of an Immunodominant Epitope in Celiac Disease

  • Chapter
Dipeptidyl Aminopeptidases in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 524))

Conclusion

An immunodominant gliadin epitope provoking celiac disease seems to be notably resistant to digestion with pepsin and pancreatic endopeptidases. This means that the capacity of the intestinal mucosa to digest it will be critical to the disease provoking capability of the peptide. We have shown that a peptide containing the immunodominant epitope is efficiently digested from the N-terminal end by dipeptidyl peptidase IV. Similar results have been obtained in a parallel work by Hausch et al.12, who in addition demonstrated that dipeptidyl carboxypeptidase I is of importance for digestion of the epitope from the C-terminal end. We have earlier demonstrated that dipeptidyl peptidase IV is low in celiac disease and also that it shows a substantial depression in patients in remission13. Even if a variation of the enzyme level is not of primary importance in the pathogenesis of the disease, it may that the relative capacity for the digestion of the peptide can be exceeded after a meal rich in wheat proteins, and thereby contribute to the development of the disease.

Best Poster Award, International Conference on Dipeptidyl Aminopeptidases, Berlin, September 2002

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Marsh, M. N., 1992, Gluten, Major Histocompatibility Complex, and the Small Intestine. A Molecular and Immunobiologic Approach to the Spectrum of Gluten Sensitivity (‘Celiac Sprue’). Gastroenterology, 102: 330–354.

    PubMed  CAS  Google Scholar 

  2. Sollid, L. M., 2000, Molecular Basis of Celiac Disease. Annu. Rev. Immunol, 18: 53–81.

    Article  PubMed  CAS  Google Scholar 

  3. Lundin, K. E.; Scott, H.; Hansen, T.; Paulsen, G. Halstensen, T. S.; Fausa, O.; Thorsby, E.; Sollid, L. M., 1993, Gliadin-Specific, HLA-DQ(Alpha l*0501, Beta 1*0201) Restricted T Cells Isolated From the Small Intestinal Mucosa of Celiac Disease Patients. J Exp. Med, 178: 187–196.

    Article  PubMed  CAS  Google Scholar 

  4. Anderson, R. P.; Degano, P.; Godkin, A. J.; Jewell, D. P.; Hill, A. V., 2000, In Vivo Antigen Challenge in Celiac Disease Identifies a Single Transglutaminase-Modified Peptide As the Dominant A-Gliadin T-Cell Epitope. Nat. Med, 6: 337–342.

    PubMed  CAS  Google Scholar 

  5. Arentz-Hansen, H.; Korner, R.; Molberg, O.; Quarsten, H.; Vader, W.; Kooy, Y. M.; Lundin, K. E.; Koning, F.; Roepstorff, P.; Sollid, L. M.; McAdam, S. N., 2000, The Intestinal T Cell Response to Alpha-Gliadin in Adult Celiac Disease Is Focused on a Single Deamidated Glutamine Targeted by Tissue Transglutaminase. J Exp. Med, 191: 603–612.

    Article  PubMed  CAS  Google Scholar 

  6. Sjöström, H.; Lundin, K. E.; Molberg, O.; Korner, R.; McAdam, S. N.; Anthonsen, D.; Quarsten, H.; Norén, O.; Roepstorff, P.; Thorsby, E.; Sollid, L. M., 1998, Identification of a Gliadin T-Cell Epitope in Coeliac Disease: General Importance of Gliadin Deamidation for Intestinal T-Cell Recognition. Scand J Immunol, 48: 111–115.

    PubMed  Google Scholar 

  7. Piper, J. L.; Gray, G. M.; Khosla, C., 2002, High Selectivity of Human Tissue Transglutaminase for Immunoactive Gliadin Peptides: Implications for Celiac Sprue. Biochemistry, 41: 386–393.

    Article  PubMed  CAS  Google Scholar 

  8. Dieterich, W.; Ehnis, T.; Bauer, M.; Donner, P.; Volta, U.; Riecken, E. O.; Schuppan, D., 1997, Identification of Tissue Transglutaminase As the Autoantigen of Celiac Disease. Nat. Med, 3: 797–801.

    Article  PubMed  CAS  Google Scholar 

  9. Schuppan, D.; Dieterich, W.; Riecken, E. O., 1998, Exposing Gliadin As a Tasty Food for Lymphocytes. Nat. Med, 4: 666–667.

    Article  PubMed  CAS  Google Scholar 

  10. Kessler, M.; Acuto, O.; Storelli, C.; Murer, H.; Muller, M.; Semenza, G., 1978, A Modified Procedure for the Rapid Preparation of Efficiently Transporting Vesicles From Small Intestinal Brush Border Membranes. Their Use in Investigating Some Properties of D-Glucose and Choline Transport Systems. Biochim. Biophys. Acta, 506: 136–154.

    PubMed  CAS  Google Scholar 

  11. Sjöström, H., 2001, Deamidation of gliadin peptides in the pathogenesis of celiac disease. In: Proocedings of the Workshop on Transglutaminases, Protein Cross-Linking and Coeliac Disease. (Mäki M, Tossavainen M. eds.) University Press, Tampere, Finland, pp. 117–122.

    Google Scholar 

  12. Hausch, F.; Shan, L.; Santiago, N. A.; Gray, G. M.; Khosla, C., 2002, Intestinal Digestive Resistance of Immunodominant Gliadin Peptides. Am. J Physiol Gastrointest. Liver Physiol, 283: G996–G1003.

    PubMed  CAS  Google Scholar 

  13. Sjöström, H.; Norén, O.; Krasilnikoff, P. A.; Gudmand-Hoyer, E., 1981, Intestinal Peptidases and Sucrase in Coeliac Disease. Clin. Chim. Acta, 109: 53–58.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Kluwer Academic Publishers

About this chapter

Cite this chapter

Koch, S., Anthonsen, D., Skovbjerg, H., Sjöström, H. (2004). On the Role of Dipeptidyl Peptidase IV in the Digestion of an Immunodominant Epitope in Celiac Disease. In: Back, N., Cohen, I.R., Kritchevsky, D., Lajtha, A., Paoletti, R. (eds) Dipeptidyl Aminopeptidases in Health and Disease. Advances in Experimental Medicine and Biology, vol 524. Springer, Boston, MA. https://doi.org/10.1007/0-306-47920-6_22

Download citation

  • DOI: https://doi.org/10.1007/0-306-47920-6_22

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-47717-1

  • Online ISBN: 978-0-306-47920-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics