IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of A-gliadin
- Author(s)
- Bateman, EAL; Ferry, BL; Hall, A; Misbah, SA; Anderson, R; Kelleher, P;
- Details
- Publication Year 2004-09,Volume 53,Issue #9,Page 1274-1278
- Journal Title
- GUT
- Publication Type
- Journal Article
- Abstract
- Background: In coeliac disease (CD) patients, the dominant DQ2-A-I-gliadin peptide recognised by CD4 T cells is contained within peptide sequence 57-73 (p57-73) of A-gliadin. This peptide sequence is also located within a 33-mer protease resistant gliadin fragment and therefore is likely to play an important role in the pathogenesis of CD. Aims: Our aim was to determine whether a B cell epitope was present within the immunodominant T cell epitope of A-gliadin and, if so, to elucidate its sequence and determine the importance of deamidation and/or modification of the amino acid at position 65 for IgA binding. Patients and methods: A cohort of CD patients, disease controls, and healthy individuals were examined. Serum IgA antibodies to the native and modified p57-73 fragment of A-gliadin were analysed using enzyme linked immunosorbent assays. Peptide scanning experiments were further used to elucidate the B cell epitope. Results and conclusion: IgA antibodies to p57-73 were found in 29/72 (40.2%) endomysial antibody positive patients, all of whom had CD. The peptide antibody appeared to be present when patients were on a diet containing gluten and declined on a gluten free diet. The p57-73 antibody was very specific for CD (98%) and had a sensitivity of 56%. The amino acid at position 65 was not important for IgA binding but was crucial for T cell recognition of p57-73. Pentapeptide PXPQP emerges as a potentially strong candidate for the IgA binding motif in this region of A-gliadin. This study shows that a significant proportion of newly diagnosed CD patients have an antibody response to the immunodominant T cell epitope.
- Publisher
- B M J PUBLISHING GROUP
- Keywords
- ALPHA-GLIADIN; B-CELL; PEPTIDE; GLUTEN; TRANSGLUTAMINASE; IDENTIFICATION; SPECTRUM
- Publisher's Version
- https://doi.org/10.1136/gut.2003.032755
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- Refer to copyright notice on published article.
Creation Date: 2004-09-01 12:00:00