IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of Α-gliadin

• Published in: Gut Vol. 53; no. 9; pp. 1274 - 1278
• Main Authors: Bateman, E A L, Ferry, B L, Hall, A, Misbah, S A, Anderson, R, Kelleher, P
• Format: Journal Article
• Language: English
• Published: BMJ Publishing Group Ltd and British Society of Gastroenterology 01-09-2004; Copyright 2004 by Gut
• Subjects: antigliadin IgA; B cell epitope; coefficient of variation; coeliac disease; ELISA; EMA; endomysial antibody; enzyme linked immunosorbent assay; GFD; gluten free diet; optical density; p57-73; paraprotein; rheumatoid factor positive; Rhf; Small Intestine; T cell epitope; TBS; Tris buffered saline; Α-gliadin peptide sequence 57-73
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2003.032755

Background: In coeliac disease (CD) patients, the dominant DQ2-Α-I-gliadin peptide recognised by CD4 T cells is contained within peptide sequence 57–73 (p57-73) of Α-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 Α-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 Α-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 Α-gliadin. This study shows that a significant proportion of newly diagnosed CD patients have an antibody response to the immunodominant T cell epitope.