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

¹ Department of Clinical Immunology, Churchill Hospital, Oxford Radcliffe Hospitals, Oxford, UK
² Department of Immunology, Chelsea and Westminster Hospital, London, UK
³ The Walter and Eliza Hall Institute, Melbourne, Australia

Correspondence to:
Correspondence to:
Dr B L Ferry
Department of Clinical Immunology, Churchill Hospital, Oxford Radcliffe Hospitals, Oxford OX3 7LJ, UK; BerneFerry{at}aol.com

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.

Abbreviations: CD, coeliac disease; p57-73, A-gliadin peptide sequence 57-73; GFD, gluten free diet; EMA, endomysial antibody; Rhf, rheumatoid factor positive; PP, paraprotein; CV, coefficient of variation; ELISA, enzyme linked immunosorbent assay; TBS, Tris buffered saline; OD, optical density

Keywords: coeliac disease; antigliadin IgA; T cell epitope; B cell epitope

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