title: HLA-DQ molecules as affinity matrix for identification of gluten T cell epitopes.
abstract: Even though MHC class II is a dominant susceptibility factor for many diseases, culprit T cell epitopes presented by disease-associated MHC molecules remain largely elusive. T cells of celiac disease lesions recognize cereal gluten epitopes presented by the disease-associated HLA molecules DQ2.5, DQ2.2, or DQ8. Employing celiac disease and complex gluten Ag digests as a model, we tested the feasibility of using DQ2.5 and DQ2.2 as an affinity matrix for identification of disease-relevant T cell epitopes. Known gluten T cell epitope peptides were enriched by DQ2.5, whereas a different set of peptides was enriched by DQ2.2. Of 86 DQ2.2-enriched peptides, four core sequences dominated. One of these core sequences is a previously known epitope and two others are novel epitopes. The study provides insight into the selection of gluten epitopes by DQ2.2. Furthermore, the approach presented is relevant for epitope identification in other MHC class II-associated disorders.
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway; Proteomics Core Facility, Oslo University Hospital-Rikshospitalet, 0027 Oslo, Norway; and siri.dorum@rr-research.no.
authors.forename: Siri
authors.initials: S
authors.lastname: Dørum
authors.affiliation: Centre for Immune Regulation, Department of Immunology, Oslo University Hospital-Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Michael
authors.initials: M
authors.lastname: Bodd
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway;
authors.forename: Lars-Egil
authors.initials: LE
authors.lastname: Fallang
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway;
authors.forename: Elin
authors.initials: E
authors.lastname: Bergseng
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway;
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Christophersen
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway;
authors.forename: Marie K
authors.initials: MK
authors.lastname: Johannesen
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway;
authors.forename: Shuo-Wang
authors.initials: SW
authors.lastname: Qiao
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway;
authors.forename: Jorunn
authors.initials: J
authors.lastname: Stamnaes
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway; Proteomics Core Facility, Oslo University Hospital-Rikshospitalet, 0027 Oslo, Norway; and.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: de Souza
authors.affiliation: Centre for Immune Regulation, Department of Immunology, University of Oslo, 0424 Oslo, Norway; Centre for Immune Regulation, Department of Immunology, Oslo University Hospital-Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Ludvig M
authors.initials: LM
authors.lastname: Sollid
mesh_terms: D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000276:immunology; D002460:Cell Line; D002850:Chromatography, Gel; D018604:Epitope Mapping / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005903:Gliadin / Q000737:chemistry / Q000276:immunology; D005983:Glutens / Q000737:chemistry / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*; D014908:Triticum / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; D010455:Peptides; D005983:Glutens; D005903:Gliadin