Celiac.com 02/16/2011 - A team of researchers recently set out to establish a universal approach to eliminate disease-triggering properties of alpha-gliadin peptides in celiac disease.
The research team included Cristina Mitea, Elma M. J. Salentijn, Peter van Veelen, Svetlana V. Goryunova, Ingrid M. van der Meer, Hetty C. van den Broeck, Jorge R. Mujico, Veronica Monserrat, Luud J. W. J. Gilissen, Jan Wouter Drijfhout, Liesbeth Dekking, Frits Koning, and Marinus J. M. Smulders.
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They are affiliated with the Department of Immunohematology and Blood Transfusion at Leiden University Medical Center, in Leiden, Plant Research International at Wageningen UR, and the Allergy Centre Wageningen, in Wageningen, The Netherlands.
Celiac disease is triggered by an uncontrolled immune response to gluten, a mix of wheat storage proteins that include α-gliadins. Research has shown that α-gliadins contain several major epitopes involved in celiac disease pathogenesis.
Eliminating such epitopes from α-gliadins would be a major step towards eliminating gluten toxicity for celiac disease patients.
The team analyzed over 3,000 expressed α-gliadin sequences from 11 types of bread wheat to figure out if they encode for peptides that might play a role in celiac disease.
The team synthesized all epitope variants they identified as peptides. They then tested each to see if it bound to the disease-associated HLA-DQ2 and HLA-DQ8 molecules, and if it was recognized by patient-derived α-gliadin specific T cell clones.
For each of the α-gliadin derived peptides involved in celiac disease, the team found several specific naturally occurring amino acid substitutions that eliminate the celiac disease-triggering properties of the epitope variants.
Finally, the team proved at the peptide level that by using systematic introduction of such naturally occurring variations α-gliadins, they can generate genes that no longer encode antigenic peptides. That is, they can create genes in wheat that do not trigger celiac disease.
Their work offers an important contribution for developing strategies to modify gluten genes in wheat so that it becomes safe for people with celiac disease and gluten intolerance.
The findings of the study also provide information for design and introduction of safe gluten genes in other cereals, which would conceivably make them both better in quality, and safe for people with celiac disease.
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