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| Article Authors: | Javier Gil-Humanes; Fernando Pistón; Stig Tollefsen; Ludvig M Sollid; Francisco Barro |
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| Article Title: | Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference. |
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| Reference ID: | 1020793 |
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| Abstract: | Celiac disease (CD) is an enteropathy triggered by the ingestion of gluten proteins from wheat and similar proteins from barley and rye. The inflammatory reaction is controlled by T cells that recognize gluten peptides in the context of human leukocyte antigen (HLA) DQ2 or HLA-DQ8 molecules. The only available treatment for the disease is a lifelong gluten-exclusion diet. We have used RNAi to down-regulate the expression of gliadins in bread wheat. A set of hairpin constructs were designed and expressed in the endosperm of bread wheat. The expression of gliadins was strongly down-regulated in the transgenic lines. Total gluten protein was extracted from transgenic lines and tested for ability to stimulate four different T-cell clones derived from the intestinal lesion of CD patients and specific for the DQ2-α-II, DQ2-γ-VII, DQ8-α-I, and DQ8-γ-I epitopes. For five of the transgenic lines, there was a 1.5-2 log reduction in the amount of the DQ2-α-II and DQ2-γ-VII epitopes and at least 1 log reduction in the amount of the DQ8-α-I and DQ8-γ-I epitopes. Furthermore, transgenic lines were also tested with two T-cell lines that are reactive with ω-gliadin epitopes. The total gluten extracts were unable to elicit T-cell responses for three of the transgenic wheat lines, and there were reduced responses for six of the transgenic lines. This work shows that the down-regulation of gliadins by RNAi can be used to obtain wheat lines with very low levels of toxicity for CD patients. |
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| Affiliations: | Instituto de Agricultura Sostenible, Consejo Superior de Investigaciones Cientificas, E-14080 Córdoba, Spain. |
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| Date: | 2010 |
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| Reference Type: | Literature |
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| PubMed ID: | 20829492 |
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| Journal: | Proc Natl Acad Sci U S A |
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| Journal Volume: | 107 |
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| Article Pages: | 17023-8 |
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| Journal ISSN: | 1091-6490 |
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| Article Chemical List: | Epitopes, T-Lymphocyte;HLA-DQ Antigens;RNA, Small Interfering;Gliadin |
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| Article MeSH List: | Base Sequence; Celiac Disease(immunology); Cell Line; Epitopes, T-Lymphocyte(genetics; immunology); Gliadin(genetics; immunology); HLA-DQ Antigens(immunology); Humans; Molecular Sequence Data; Nucleic Acid Conformation; Plants, Genetically Modified(genetics; immunology); RNA Interference; RNA, Small Interfering(chemistry; genetics); T-Lymphocytes(immunology); Triticum(genetics; immunology) |
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| Curation Last Updated: | 2013-04-25 20:10:18 |
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