Epitopes described in "The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides."

Article Authors:Willemijn Vader; Yvonne Kooy; Peter Van Veelen; Arnoud De Ru; Diana Harris; Willemien Benckhuijsen; Salvador Peña; Luisa Mearin; Jan Wouter Drijfhout; Frits Koning
Article Title:The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides.
Reference Detail
Reference ID:1005489
Abstract:BACKGROUND & AIMS: 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.
Affiliations:Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
Reference Type:Literature
PubMed ID:12055577
Journal Volume:122
Article Pages:1729-37
Journal ISSN:0016-5085
Article Chemical List:Epitopes;HLA-DQ Antigens;HLA-DQ2 antigen;Peptide Fragments;Glutens;Gliadin;glutenin
Article MeSH List:Amino Acid Sequence; Celiac Disease(immunology); Cell Line; Child; Child, Preschool; Epitopes; Gliadin(immunology); Glutens(analogs & derivatives; genetics; immunology); HLA-DQ Antigens(analysis); Humans; Infant; Peptide Fragments(genetics; immunology); T-Lymphocytes(immunology)
Curation Last Updated:2014-10-03 20:41:12