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

  • Sina Koch
  • Dorit Anthonsen
  • Hanne Skovbjerg
  • Hans Sjöström
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 524)


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.


Celiac Disease Coeliac Disease Celiac Disease Patient Dipeptidyl Peptidase Immunodominant Epitope 
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  1. 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.PubMedGoogle Scholar
  2. 2.
    Sollid, L. M., 2000, Molecular Basis of Celiac Disease. Annu. Rev. Immunol, 18: 53–81.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 9.
    Schuppan, D.; Dieterich, W.; Riecken, E. O., 1998, Exposing Gliadin As a Tasty Food for Lymphocytes. Nat. Med, 4: 666–667.PubMedCrossRefGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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. 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.PubMedGoogle Scholar
  13. 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.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Sina Koch
    • 1
  • Dorit Anthonsen
    • 1
  • Hanne Skovbjerg
    • 1
  • Hans Sjöström
    • 1
  1. 1.Biochemistry Laboratory C, Department of Medical Biochemistry and Genetics, The Panum InstituteUniversity of CopenhagenCopenhagenDenmark

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