Epitopes described in "Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference."

Article Authors:Javier Gil-Humanes; Fernando Pistón; Stig Tollefsen; Ludvig M Sollid; Francisco Barro
Article Title:Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference.
Reference Detail
Reference ID:1020793
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--II, DQ2--VII, DQ8--I, and DQ8--I epitopes. For five of the transgenic lines, there was a 1.5-2 log reduction in the amount of the DQ2--II and DQ2--VII epitopes and at least 1 log reduction in the amount of the DQ8--I and DQ8--I epitopes. Furthermore, transgenic lines were also tested with two T-cell lines that are reactive with -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.
Affiliations:Instituto de Agricultura Sostenible, Consejo Superior de Investigaciones Cientificas, E-14080 Córdoba, Spain.
Reference Type:Literature
PubMed ID:20829492
Journal:Proc Natl Acad Sci U S A
Journal Volume:107
Article Pages:17023-8
Journal ISSN:0027-8424
Article Chemical List:Epitopes, T-Lymphocyte;HLA-DQ Antigens;RNA, Small Interfering;Gliadin
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)
Curation Last Updated:2015-06-07 20:01:21