Author: Anderson, R.P.; Degano, P.; Godkin, A.J.; Jewell, D.P.; Hill, A.V.
Description: 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.
Subject Headings: Adult; Age of Onset; Amino Acid Sequence; Celiac Disease/epidemiology/genetics/immunology; Cells, Cultured; Epitopes/chemistry/immunology; Female; Gliadin/chemistry/immunology/pharmacology; 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; United Kingdom/epidemiology
Keywords: In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope
Publication year: 2000
Journal or book title: Nature Medicine
Volume: 6
Issue: 3
Pages: 337-342
Find the full text : https://www.nature.com/articles/nm0300_337
Find more like this one (cited by): https://scholar.google.com/scholar?cites=8991732398900151127&as_sdt=1000005&sciodt=0,16&hl=en
Type: Journal Article
Serial number: 2522