Epitopes described in "HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease."

Article Authors:Stig Tollefsen; Helene Arentz-Hansen; Burkhard Fleckenstein; Oyvind Molberg; Melinda Ráki; William W Kwok; Günther Jung; Knut E A Lundin; Ludvig M Sollid
Article Title:HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease.
Reference Detail
Reference ID:1005072
Abstract:Celiac disease is associated with HLA-DQ2 and, to a lesser extent, HLA-DQ8. Type 1 diabetes is associated with the same DQ molecules in the opposite order and with possible involvement of trans-encoded DQ heterodimers. T cells that are reactive with gluten peptides deamidated by transglutaminase 2 and invariably restricted by DQ2 or DQ8 can be isolated from celiac lesions. We used intestinal T cells from celiac patients to map DQ2 and DQ8 epitopes within 2 representative gluten proteins, alpha-gliadin AJ133612 and gamma-gliadin M36999. For alpha-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of 2 separate regions. For gamma-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of the same region. Some gamma-gliadin peptides were recognized by T cells in the context of DQ2 or DQ8 when bound in exactly the same registers, but with different requirements for deamidation; deamidation at peptide position 4 (P4) was important for DQ2-restricted T cells, whereas deamidation at P1 and/or P9 was important for DQ8-restricted T cells. Peptides combining the DQ2 and DQ8 signatures could be presented by DQ2, DQ8, and trans-encoded DQ heterodimers. Our findings shed light on the basis for the HLA associations in celiac disease and type 1 diabetes.
Affiliations:Institute of Immunology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
Reference Type:Literature
PubMed ID:16878175
Journal:J Clin Invest
Journal Volume:116
Article Pages:2226-36
Journal ISSN:0021-9738
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@6f5186f1;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5172714f;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@306d234f;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4d29305f;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4b26d48c;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@624c59df;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2a071e4
Article MeSH List:Amino Acid Sequence; Celiac Disease(immunology); Diabetes Mellitus, Type 1(genetics; immunology); Dimerization; Epitopes(chemistry); Gliadin(chemistry; genetics); HLA Antigens(genetics; immunology); HLA-DQ Antigens(chemistry; genetics); Humans; Immunity, Mucosal; Molecular Sequence Data; Peptide Fragments(chemistry); T-Lymphocytes(immunology)
Curation Last Updated:2015-01-17 21:39:58