Type:

Other

Description:

Celiac disease is a T cell-driven intolerance to wheat gluten. The gluten-derived T cell epitopes are proline-rich and thereby highly resistant to proteolytic degradation within the gastrointestinal tract. Oral supplementation with prolyl oligopeptidases has therefore been proposed as a potential therapeutic approach. The enzymes studied, however, have limitations as they are irreversibly inactivated by pepsin and acidic pH, both present in the stomach. As a consequence, these enzymes will fail to degrade gluten before it reaches the small intestine, the site where gluten induces inflammatory T cell responses that lead to celiac disease. We have now determined the usefulness of a newly identified prolyl endoprotease from Aspergillus niger for this purpose. Gluten and its peptic/tryptic digest were treated with prolyl endoprotease, and the destruction of the T cell epitopes was tested using mass spectrometry, T cell proliferation assays, ELISA, reverse-phase HPLC, SDS-PAGE, and Western blotting. We observed that the A. niger prolyl endoprotease works optimally at 4–5 pH, remains stable at 2 pH, and is completely resistant to digestion with pepsin. Moreover, the A. niger-derived enzyme efficiently degraded all tested T cell stimulatory peptides as well as intact gluten molecules. On average, the endoprotease from A. niger degraded gluten peptides 60 times faster than a prolyl oligopeptidase. Together these results indicate that the enzyme from A. niger efficiently degrades gluten proteins. Future studies are required to determine if the prolyl endoprotease can be used as an oral supplement to reduce gluten intake in patients.

Subjects:

  • Education > General

Education Levels:

    Keywords:

    oai:nsdl.org:2200/20100927010240884T,NSDL,NSDL_SetSpec_BEN,T cell,Education,Immune system,Life Science,Teacher-centered/traditional instruction,Tutorial or self-directed instruction,Student-centered instruction

    Language:

    English

    Access Privileges:

    Public - Available to anyone

    License Deed:

    Creative Commons Attribution Non-Commercial Share Alike

    Collections:

    None
    This resource has not yet been aligned.
    Curriki Rating
    'NR' - This resource has not been rated
    NR
    'NR' - This resource has not been rated

    This resource has not yet been reviewed.

    Not Rated Yet.

    Non-profit Tax ID # 203478467