Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-3-22
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1078-8956
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
337-42
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10700238-Adult, pubmed-meshheading:10700238-Age of Onset, pubmed-meshheading:10700238-Amino Acid Sequence, pubmed-meshheading:10700238-Celiac Disease, pubmed-meshheading:10700238-Cells, Cultured, pubmed-meshheading:10700238-Epitopes, pubmed-meshheading:10700238-Female, pubmed-meshheading:10700238-Gliadin, pubmed-meshheading:10700238-Great Britain, pubmed-meshheading:10700238-HLA-DQ Antigens, pubmed-meshheading:10700238-Humans, pubmed-meshheading:10700238-Interferon-gamma, pubmed-meshheading:10700238-Interleukin-10, pubmed-meshheading:10700238-Lymphocyte Activation, pubmed-meshheading:10700238-Lymphocytes, pubmed-meshheading:10700238-Male, pubmed-meshheading:10700238-Middle Aged, pubmed-meshheading:10700238-Molecular Sequence Data, pubmed-meshheading:10700238-Peptide Fragments, pubmed-meshheading:10700238-Prevalence, pubmed-meshheading:10700238-T-Lymphocytes, pubmed-meshheading:10700238-Transglutaminases
pubmed:year
2000
pubmed:articleTitle
In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope.
pubmed:affiliation
Institute of Molecular Medicine, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK. bob.anderson@ndm.ox.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't