title: Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes.
abstract: 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 alpha-gliadins contain several peptides that are associated to the disease.
  
  
  RESULTS
  We obtained 230 distinct alpha-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 alpha-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, alpha-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-alpha9 and glia-alpha20, but never the intact epitopes glia-alpha and glia-alpha2. 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.
  
  
  CONCLUSIONS
  Our analysis shows that alpha-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.
authors.affiliation: Allergy Consortium Wageningen, PO Box 16, NL-6700 AA Wageningen, The Netherlands. teun.vanherpen@wur.nl
authors.forename: Teun W J M
authors.initials: TW
authors.lastname: van Herpen
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Goryunova
authors.forename: Johanna
authors.initials: J
authors.lastname: van der Schoot
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
authors.forename: Elma
authors.initials: E
authors.lastname: Salentijn
authors.forename: Oscar
authors.initials: O
authors.lastname: Vorst
authors.forename: Martijn F
authors.initials: MF
authors.lastname: Schenk
authors.forename: Peter A
authors.initials: PA
authors.lastname: van Veelen
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
authors.forename: Loek J M
authors.initials: LJ
authors.lastname: van Soest
authors.forename: Ben
authors.initials: B
authors.lastname: Vosman
authors.forename: Dirk
authors.initials: D
authors.lastname: Bosch
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Hamer
authors.forename: Luud J W J
authors.initials: LJ
authors.lastname: Gilissen
authors.forename: Marinus J M
authors.initials: MJ
authors.lastname: Smulders
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002446:Celiac Disease / Q000276:immunology*; D003001:Cloning, Molecular; D018744:DNA, Plant / Q000235:genetics; D000939:Epitopes / Q000235:genetics*; D019143:Evolution, Molecular; D018745:Genome, Plant; D005903:Gliadin / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010455:Peptides / Q000235:genetics; D010802:Phylogeny; D011003:Ploidies; D011544:Pseudogenes; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014908:Triticum / Q000145:classification / Q000235:genetics*
chemical_list: D018744:DNA, Plant; D000939:Epitopes; D010455:Peptides; C097188:polyglutamine; D005903:Gliadin