title: Diversification of the celiac disease α-gliadin complex in wheat: a 33-mer peptide with six overlapping epitopes, evolved following polyploidization.
abstract: The gluten proteins from wheat, barley and rye are responsible both for celiac disease (CD) and for non-celiac gluten sensitivity, two pathologies affecting up to 6-8% of the human population worldwide. The wheat α-gliadin proteins contain three major CD immunogenic peptides: p31-43, which induces the innate immune response; the 33-mer, formed by six overlapping copies of three highly stimulatory epitopes; and an additional DQ2.5-glia-α3 epitope which partially overlaps with the 33-mer. Next-generation sequencing (NGS) and Sanger sequencing of α-gliadin genes from diploid and polyploid wheat provided six types of α-gliadins (named 1-6) with strong differences in their frequencies in diploid and polyploid wheat, and in the presence and abundance of these CD immunogenic peptides. Immunogenic variants of the p31-43 peptide were found in most of the α-gliadins. Variants of the DQ2.5-glia-α3 epitope were associated with specific types of α-gliadins. Remarkably, only type 1 α-gliadins contained 33-mer epitopes. Moreover, the full immunodominant 33-mer fragment was only present in hexaploid wheat at low abundance, probably as the result of allohexaploidization events from subtype 1.2 α-gliadins found only in Aegilops tauschii, the D-genome donor of hexaploid wheat. Type 3 α-gliadins seem to be the ancestral type as they are found in most of the α-gliadin-expressing Triticeae species. These findings are important for reducing the incidence of CD by the breeding/selection of wheat varieties with low stimulatory capacity of T cells. Moreover, advanced genome-editing techniques (TALENs, CRISPR) will be easier to implement on the small group of α-gliadins containing only immunogenic peptides.
authors: Departamento de Mejora Genética, Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Córdoba, E-14080, Spain.
authors: Carmen V
authors: CV
authors: Ozuna
authors: Departamento de Mejora Genética, Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Córdoba, E-14080, Spain.
authors: Julio C M
authors: JC
authors: Iehisa
authors: Departamento de Mejora Genética, Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Córdoba, E-14080, Spain.
authors: María J
authors: MJ
authors: Giménez
authors: Departamento de Genética, Escuela Superior de Ingenieros Agrónomos y Montes, Universidad de Córdoba, Córdoba, E-14071, Spain.
authors: Juan B
authors: http://orcid.org/0000-0002-7036-1317
authors: JB
authors: Alvarez
authors: Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, 41012, Spain.
authors: Carolina
authors: C
authors: Sousa
authors: Departamento de Mejora Genética, Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Córdoba, E-14080, Spain.
authors: Francisco
authors: F
authors: Barro
mesh_terms: D002446:Celiac Disease / Q000276:immunology*; D003001:Cloning, Molecular; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D005903:Gliadin / Q000235:genetics / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011123:Polyploidy; D011544:Pseudogenes; D014908:Triticum / Q000235:genetics* / Q000276:immunology*
chemical_list: D000939:Epitopes; D005903:Gliadin
keywords: 33-mer peptide; alpha-gliadin; celiac disease; wheat