title: Glutenin is involved in the gluten-driven mucosal T cell response.
abstract: Gluten ingestion causes coeliac disease in susceptible individuals. Gluten is a heterogeneous mixture of glutenin and gliadin, the latter of which is considered responsible for disease induction. By combining high-performance liquid chromatography purification steps of gluten with a T cell bioassay and mass spectral analyses, we have identified a glutenin peptide (glt04 707-742) that activates T cells from the small intestine of a coeliac disease patient and results in the secretion of large amounts of IFN-gamma. The minimal T cell stimulatory core of the peptide (residues 724-734) is repetitively present in glutenin molecules. Moreover, it was observed that a large number of naturally occurring variants of this peptide are recognized by the T cells. These data suggest that the large heterogeneity of glutenin proteins dramatically increases the number of available T cell epitopes. Together, the results provide new insight into the nature of the gluten antigens that lead to coeliac disease and suggest that glutenin, next to gliadin-derived antigens, may be involved in the disease process.
authors.affiliation: Department of Immunohaematology and Bloodbank, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: van de Wal
authors.forename: Y M
authors.initials: YM
authors.lastname: Kooy
authors.forename: P
authors.initials: P
authors.lastname: van Veelen
authors.forename: W
authors.initials: W
authors.lastname: Vader
authors.forename: S A
authors.initials: SA
authors.lastname: August
authors.forename: J W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: S A
authors.initials: SA
authors.lastname: Peña
authors.forename: F
authors.initials: F
authors.lastname: Koning
mesh_terms: D000595:Amino Acid Sequence; D002447:Celiac Plexus / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D005983:Glutens / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010449:Peptide Mapping; D013601:T-Lymphocytes / Q000276:immunology*; D014908:Triticum / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; D010446:Peptide Fragments; D005983:Glutens; C037302:glutenin