- S.V. Goryunova (1)
- V. Goryunova-Svetlana (2)
- R.J. Hamer (1)
- T.W.J.M. Herpen van (2)
- H.D. Jones (1)
- H.H. Jonker (1)
- F. Koning de (3)
- Y. Kooy-Winkelaar (1)
- I.M. Meer van der (1)
- C. Mitea (2)
- M. Mitreva (1)
- V. Monserrat (1)
- J.R. Mujico (2)
- M. Riley (1)
- A. Ru (1)
- E.M.J. Salentijn (3)
- M.F. Schenk (1)
- J. Schoot van der (1)
- P.R. Shewry (1)
- M.J.M. Smulders (5)
- L.J.M. Soest van (2)
- L. Spaenij-Dekking (1)
- C. Sparks (1)
- P. Veelen van (5)
- O.F.J. Vorst (1)
- B.J. Vosman (1)
Natural variation in avenin epitopes among oat varieties: implications for Celiac
Mujico, J.R. ; Mitea, C. ; Gilissen, L.J.W.J. ; Ru, A. ; Veelen, P. van; Smulders, M.J.M. ; Koning, F. de - \ 2011
Journal of Cereal Science 54 (2011)1. - ISSN 0733-5210 - p. 8 - 12.
t-cells - gliadin - gluten - wheat - peptides - prevalence - antibodies - toxicity - children - hla-dq2
Celiac disease (CD) is a chronic inflammatory disease affecting the small intestinal mucosa. The causative agents have been identified as gluten proteins from wheat, barley and rye, and the only available treatment for CD patients is a lifelong gluten-free diet. Non-gluten containing cereals would be a valuable contribution to the gluten-free diet. In this respect, oats are a good choice. However, commercial lots of oat flakes and flour frequently are contaminated with wheat, barley and rye, and two studies have reported that some peptides derived from the gluten-like avenin storage proteins of oat can trigger an immune response in some CD patients. In the present study we have initiated the investigation whether all oat varieties contain similar amounts of potentially harmful sequences by biochemical and immunological methods. We confirm that commercial oat preparations are contaminated with other cereals that contain gluten or gluten-like proteins. Moreover, our results demonstrate that contamination-free oat varieties differ in their capacity to stimulate an avenin-sensitive gamma-gliadin specific T cell line derived from a patient with CD, indicative for differences in the two known avenin epitopes among oat varieties, implying that selection and breeding of completely safe oat varieties for all CD patients may be a realistic possibility.
A universal approach to eliminate antigenic properties of alpha-gliadin peptides in celiac disease
Mitea, C. ; Salentijn, E.M.J. ; Veelen, P. van; Goryunova-Svetlana, V. ; Meer, I.M. van der; Broeck, H.C. van den; Mujico, J.R. ; Monserrat, V. ; Gilissen, L.J.W.J. ; Drijfhout, J.W. ; Dekking, L. ; Smulders, M.J.M. - \ 2010
PLoS ONE 5 (2010). - ISSN 1932-6203 - 12 p.
t-cell response - tissue transglutaminase - cereal toxicity - wheat - epitopes - arabidopsis - mutagenesis - prevalence - varieties - explains
Celiac disease is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins, including the a-gliadins. It has been shown that a-gliadins harbor several major epitopes involved in the disease pathogenesis. A major step towards elimination of gluten toxicity for celiac disease patients would thus be the elimination of such epitopes from a-gliadins. We have analyzed over 3,000 expressed a-gliadin sequences from 11 bread wheat cultivars to determine whether they encode for peptides potentially involved in celiac disease. All identified epitope variants were synthesized as peptides and tested for binding to the disease-associated HLA-DQ2 and HLA-DQ8 molecules and for recognition by patient-derived a-gliadin specific T cell clones. Several specific naturally occurring amino acid substitutions were identified for each of the a-gliadin derived peptides involved in celiac disease that eliminate the antigenic properties of the epitope variants. Finally, we provide proof of principle at the peptide level that through the systematic introduction of such naturally occurring variations a-gliadins genes can be generated that no longer encode antigenic peptides. This forms a crucial step in the development of strategies to modify gluten genes in wheat so that it becomes safe for celiac disease patients. It also provides the information to design and introduce safe gluten genes in other cereals, which would exhibit improved quality while remaining safe for consumption by celiac disease patients.
|Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes
Herpen, T.W.J.M. van; Goryunova, S.V. ; Salentijn, E.M.J. ; Riley, M. ; Sparks, C. ; Veelen, P. van; Bosch, H.J. ; Gilissen, L.J.W.J. ; Smulders, M.J.M. ; Jones, H.D. ; Shewry, P.R. ; Hamer, R.J. - \ 2007
In: Gluten Proteins 2006 / Lookhart, G.L., St. Paul, Minnesota : AAAC International - ISBN 9781891127571 - p. 321 - 325.
Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes
Herpen, T.W.J.M. van; Goryunova-Svetlana, V. ; Schoot, J. van der; Mitreva, M. ; Salentijn, E.M.J. ; Vorst, O.F.J. ; Schenk, M.F. ; Veelen, P. van; Koning, F. de; Soest, L.J.M. van; Vosman, B.J. ; Bosch, H.J. ; Gilissen, L.J.W.J. ; Smulders, M.J.M. - \ 2006
BMC Genomics 7 (2006). - ISSN 1471-2164
tissue transglutaminase - hexaploid wheat - cereal toxicity - t-cells - dna - evolution - peptides - family - loci
Background - Bread wheat (Triticum aestivum) is an important staple food. However, wheat gluten proteins cause celiac disease (CD) in 0.5 to 1% of the general population. Among these proteins, the a-gliadins contain several peptides that are associated to the disease. Results - We obtained 230 distinct a-gliadin gene sequences from severaldiploid wheat species representing the ancestral A, B, and D genomes of the hexaploid bread wheat. The large majority of these sequences (87%) contained an internal stop codon. All a-gliadin sequences could be distinguished according to the genome of origin on the basis of sequence similarity, of the average length of the polyglutamine repeats, and of the differences in the presence of four peptides that have been identified as T cell stimulatory epitopes in CD patients through binding to HLA-DQ2/8. By sequence similarity, a-gliadins from the public database of hexaploid T. aestivum could be assigned directly to chromosome 6A, 6B, or 6D. T. monococcum (A genome) sequences, as well as those from chromosome 6A of bread wheat, almost invariably contained epitope glia-a9 and glia-a20, but never the intact epitopes glia-a and glia-a2. A number of sequences from T. speltoides, as well as a number of sequences fromchromosome 6B of bread wheat, did not contain any of the four T cell epitopes screened for. The sequences from T. tauschii (D genome), as well as those from chromosome 6D of bread wheat, were found to contain all of these T cell epitopes in variable combinations per gene. The differences in epitope composition resulted mainly from point mutations. These substitutions appeared to be genome specific. Conclusion - Our analysis shows that a-gliadin sequences from the three genomes of bread wheat form distinct groups. The four known T cell stimulatory epitopes are distributed non-randomly across the sequences, indicating that the three genomes contribute differently to epitope content. A systematic analysis of all known epitopes in gliadins and glutenins will lead to better understanding of the differences in toxicity among wheat varieties. On the basis of such insight, breeding strategies can be designed to generate less toxic varieties of wheat which may be tolerated by at least part of the CD patient population.
Natural variation in toxicity of wheat: potential for selection of nontoxic varieties for celiac disease patients
Spaenij-Dekking, L. ; Kooy-Winkelaar, Y. ; Veelen, P. van; Drijfhout, J.W. ; Jonker, H.H. ; Soest, L.J.M. van; Smulders, M.J.M. ; Bosch, H.J. ; Gilissen, L.J.W.J. ; Koning, F. de - \ 2005
Gastroenterology 129 (2005)3. - ISSN 0016-5085 - p. 797 - 806.
t-cell recognition - tissue transglutaminase - prolyl endopeptidase - gliadin peptides - interferon-gamma - cereal toxicity - alpha-gliadin - in-vivo - gluten - epitopes
Background & Aims: Celiac disease (CD) is an intestinal disorder caused by T-cell responses to peptides derived from the gluten proteins present in wheat. Such peptides have been found both in the gliadin and glutenin proteins in gluten. The only cure for CD is a lifelong gluten-free diet. It is unknown, however, if all wheat varieties are equally harmful for patients. We investigated whether wheat varieties exist with a natural low number of T-cell¿stimulatory epitopes. Methods: Gluten proteins present in public databases were analyzed for the presence of T-cell¿stimulatory sequences. In addition, wheat accessions from diploid (AA, SS/BB, and DD genomes), tetraploid (AABB), and hexaploid (AABBDD) Triticum species were tested for the presence of T-cell¿stimulatory epitopes in gliadins and glutenins by both T-cell and monoclonal antibody¿based assays. Results: The database analysis readily identified gluten proteins that lack 1 or more of the known T-cell¿stimulatory sequences. Moreover, both the T-cell¿ and antibody-based assays showed that a large variation exists in the amount of T-cell¿stimulatory peptides present in the wheat accessions. Conclusions: Sufficient genetic variation is present to endeavor the selection of wheat accessions that contain low amounts of T-cell¿stimulatory sequences. Such materials may be used to select and breed wheat varieties suitable for consumption by CD patients, contributing to a well-balanced diet and an increase in their quality of life. Such varieties also may be useful for disease prevention in individuals at risk.