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Intestinal digestive resistance of immunodominant gliadin peptides

Intestinal digestive resistance of immunodominant gliadin peptides Abstract Two recently identified immunodominant epitopes from α-gliadin account for most of the stimulatory activity of dietary gluten on intestinal and peripheral T lymphocytes in patients with celiac sprue. The proteolytic kinetics of peptides containing these epitopes were analyzed in vitro using soluble proteases from bovine and porcine pancreas and brush-border membrane vesicles from adult rat intestine. We showed that these proline-glutamine-rich epitopes are exceptionally resistant to enzymatic processing. Moreover, as estimated from the residual peptide structure and confirmed by exogeneous peptidase supplementation, dipeptidyl peptidase IV and dipeptidyl carboxypeptidase I were identified as the rate-limiting enzymes in the digestive breakdown of these peptides. A similar conclusion also emerged from analogous studies with brush-border membrane from a human intestinal biopsy. Supplementation of rat brush-border membrane with trace quantities of a bacterial prolyl endopeptidase led to the rapid destruction of the immunodominant epitopes in these peptides. These results suggest a possible enzyme therapy strategy for celiac sprue, for which the only current therapeutic option is strict exclusion of gluten-containing food. celiac sprue brush-border membrane peptidase prolyl endopeptidase kinetics Footnotes This research was supported by the 1999 Alan T. Waterman Award from the National Science Foundation (to C. Khosla). Address for reprint requests and other correspondence: C. Khosla, Stanford University, Dept. of Chemical Engineering, 380 Roth Way, Keck Science Bldg., Rm. 389, Stanford, CA 94305-5025 (E-mail: ck@chemeng.stanford.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. June 5, 2002;10.1152/ajpgi.00136.2002 Copyright © 2002 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

Intestinal digestive resistance of immunodominant gliadin peptides

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References (29)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
DOI
10.1152/ajpgi.00136.2002
pmid
12223360
Publisher site
See Article on Publisher Site

Abstract

Abstract Two recently identified immunodominant epitopes from α-gliadin account for most of the stimulatory activity of dietary gluten on intestinal and peripheral T lymphocytes in patients with celiac sprue. The proteolytic kinetics of peptides containing these epitopes were analyzed in vitro using soluble proteases from bovine and porcine pancreas and brush-border membrane vesicles from adult rat intestine. We showed that these proline-glutamine-rich epitopes are exceptionally resistant to enzymatic processing. Moreover, as estimated from the residual peptide structure and confirmed by exogeneous peptidase supplementation, dipeptidyl peptidase IV and dipeptidyl carboxypeptidase I were identified as the rate-limiting enzymes in the digestive breakdown of these peptides. A similar conclusion also emerged from analogous studies with brush-border membrane from a human intestinal biopsy. Supplementation of rat brush-border membrane with trace quantities of a bacterial prolyl endopeptidase led to the rapid destruction of the immunodominant epitopes in these peptides. These results suggest a possible enzyme therapy strategy for celiac sprue, for which the only current therapeutic option is strict exclusion of gluten-containing food. celiac sprue brush-border membrane peptidase prolyl endopeptidase kinetics Footnotes This research was supported by the 1999 Alan T. Waterman Award from the National Science Foundation (to C. Khosla). Address for reprint requests and other correspondence: C. Khosla, Stanford University, Dept. of Chemical Engineering, 380 Roth Way, Keck Science Bldg., Rm. 389, Stanford, CA 94305-5025 (E-mail: ck@chemeng.stanford.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. June 5, 2002;10.1152/ajpgi.00136.2002 Copyright © 2002 the American Physiological Society

Journal

AJP - Gastrointestinal and Liver PhysiologyThe American Physiological Society

Published: Oct 1, 2002

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