Epitopes described in "In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope."

Article Authors:R P Anderson; P Degano; A J Godkin; D P Jewell; A V Hill
Article Title:In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope.
Reference Detail
Reference ID:315349
Abstract:Celiac disease (CD) is an increasingly diagnosed enteropathy (prevalence, 1:200-1:300) that is induced by dietary exposure to wheat gliadins (as well as related proteins in rye and barley) and is strongly associated with HLA-DQ2 (alpha1*0501, beta1*0201), which is present in over 90% of CD patients. Because a variety of gliadin peptides have been identified as epitopes for gliadin-specific T-cell clones and as bioactive sequences in feeding studies and in ex vivo CD intestinal biopsy challenge, it has been unclear whether a 'dominant' T-cell epitope is associated with CD. Here, we used fresh peripheral blood lymphocytes from individual subjects undergoing short-term antigen challenge and tissue transglutaminase-treated, overlapping synthetic peptides spanning A-gliadin to demonstrate a transient, disease-specific, DQ2-restricted, CD4 T-cell response to a single dominant epitope. Optimal gamma interferon release in an ELISPOT assay was elicited by a 17-amino-acid peptide corresponding to the partially deamidated peptide of A-gliadin amino acids 57-73 (Q65E). Consistent with earlier reports indicating that host tissue transglutaminase modification of gliadin enhances gliadin-specific CD T-cell responses, tissue transglutaminase specifically deamidated Q65 in the peptide of A-gliadin amino acids 56-75. Discovery of this dominant epitope may allow development of antigen-specific immunotherapy for CD.
Affiliations:Institute of Molecular Medicine, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK. bob.anderson@ndm.ox.ac.uk
Reference Type:Literature
PubMed ID:10700238
Journal:Nat Med
Journal Volume:6
Article Pages:337-42
Journal ISSN:1078-8956
Article Chemical List:Epitopes;HLA-DQ Antigens;HLA-DQ2 antigen;Peptide Fragments;Interleukin-10;Interferon-gamma;Gliadin;Transglutaminases
Article MeSH List:Adult; Age of Onset; Amino Acid Sequence; Celiac Disease(epidemiology; genetics; immunology); Cells, Cultured; Epitopes(chemistry; immunology); Female; Gliadin(chemistry; immunology; pharmacology); Great Britain(epidemiology); HLA-DQ Antigens(genetics; immunology); Humans; Interferon-gamma(biosynthesis); Interleukin-10(biosynthesis); Lymphocyte Activation; Lymphocytes(drug effects; immunology); Male; Middle Aged; Molecular Sequence Data; Peptide Fragments(immunology; pharmacology); Prevalence; T-Lymphocytes(immunology); Transglutaminases(metabolism)
Article Comments:Data originally imported from the Database of Functional Molecular Immunology, FIMM (http://sdmc.lit.org.sg:8080/fimm/)
Curation Last Updated:2015-01-27 18:00:30