Mapping of gluten T-cell epitopes in the bread wheat ancestors: implications for celiac disease.
OBJECTIVE
Celiac disease is a prevalent disorder characterized by a chronic intestinal inflammation driven by HLA-DQ2 or -DQ8-restricted T cells specific for ingested wheat gluten peptides. The dominant T-cell responses are to epitopes that cluster within a stable 33mer fragment formed by physiologic digestion of distinct alpha-gliadins. Celiac disease is treated by excluding all gluten proteins from the diet. Conceivably, a diet based on baking-quality gluten from a wheat species that expresses no or few T-cell stimulatory gluten peptides should be equally well tolerated by the celiac patients and, importantly, also be beneficial for disease prevention.


METHODS
To identify baking quality, harmless wheat, we followed the evolution of the wheat back to the species that most likely have contributed the AA, BB, and DD genomes to the bread wheat. Gluten were extracted from a large collection of these ancient wheat species and screened for T-cell stimulatory gluten peptides.


RESULTS
Distinct differences in the intestinal T-cell responses to the diploid species were identified. Interestingly, we found that the fragments identical or equivalent to the immunodominant 33mer fragment are encoded by alpha-gliadin genes on the wheat chromosome 6D and thus absent from gluten of diploid einkorn (AA) and even certain cultivars of the tetraploid (AABB) pasta wheat.


CONCLUSIONS
These findings have implications for celiac disease because they raise the prospect of identifying or producing by breeding wheat species with low or absent levels of harmful gluten proteins.
Molberg
Oyvind
O
Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway. oyvind.molberg@medisin.uio.no
Uhlen
Anne Kjersti
AK
Jensen
Tore
T
Flaete
Nina Solheim
NS
Fleckenstein
Burkhard
B
Arentz-Hansen
Helene
H
Raki
Melinda
M
Lundin
Knut E A
KE
Sollid
Ludvig M
LM
D000595:Amino Acid Sequence; D001939:Bread; D002446:Celiac Disease / Q000209:etiology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005983:Glutens / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*; D014908:Triticum / Q000235:genetics
D000939:Epitopes; D010446:Peptide Fragments; D005983:Glutens