title: The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides.
abstract: OBJECTIVE
  Gluten (GLU)-specific T-cell responses in HLA-DQ2 positive adult celiac disease (CD) patients are directed to an immunodominant alpha-gliadin (GLIA) peptide that requires deamidation for T-cell recognition. The aim of the current study was to determine which GLU peptide(s) are involved early in disease.
  
  
  METHODS
  We have characterized the GLU-specific T-cell response in HLA-DQ2 positive children with recent onset CD.
  
  
  RESULTS
  We found that 50% of these patients do not respond to the alpha-GLIA peptide but to a diverse set of GLIA and glutenin (GLT) peptides, including 6 novel epitopes. Moreover, individual patients respond to distinct (combinations of) GLU peptides. T-cell cross-reactivity toward homologous GLIA and GLT peptides was observed, which might play a role in the initial spreading of the GLU-specific T-cell response. Although all pediatric patients displayed deamidation-dependent responses, deamidation-independent responses were found in the majority of patients as well. Finally, T-cell responses to 3 of these novel GLU peptides were found in adult CD patients.
  
  
  CONCLUSIONS
  The diversity of the GLU-specific T-cell response is far greater than was previously appreciated. Both adult and young CD patients can respond to a diverse repertoire of GLU peptides. The observation that T-cell responses to 3 of the novel peptides are independent of deamidation indicates that T-cell responses can be initiated toward native GLU peptides. The possibility that deamidation drives the GLU response toward immunodominant T-cell stimulatory peptides after disease initiation is discussed.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Willemijn
authors.initials: W
authors.lastname: Vader
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kooy
authors.forename: Peter
authors.initials: P
authors.lastname: Van Veelen
authors.forename: Arnoud
authors.initials: A
authors.lastname: De Ru
authors.forename: Diana
authors.initials: D
authors.lastname: Harris
authors.forename: Willemien
authors.initials: W
authors.lastname: Benckhuijsen
authors.forename: Salvador
authors.initials: S
authors.lastname: Peña
authors.forename: Luisa
authors.initials: L
authors.lastname: Mearin
authors.forename: Jan Wouter
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
mesh_terms: D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000276:immunology*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D000939:Epitopes; D005903:Gliadin / Q000276:immunology*; D005983:Glutens / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000032:analysis; D006801:Humans; D007223:Infant; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000939:Epitopes; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D010446:Peptide Fragments; D005983:Glutens; D005903:Gliadin; C037302:glutenin