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Gut 53:1274-1278 doi:10.1136/gut.2003.032755
  • Small intestine

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

  1. E A L Bateman1,
  2. B L Ferry1,
  3. A Hall2,
  4. S A Misbah1,
  5. R Anderson3,
  6. P Kelleher2
  1. 1Department of Clinical Immunology, Churchill Hospital, Oxford Radcliffe Hospitals, Oxford, UK
  2. 2Department of Immunology, Chelsea and Westminster Hospital, London, UK
  3. 3The Walter and Eliza Hall Institute, Melbourne, Australia
  1. Correspondence to:
    Dr B L Ferry
    Department of Clinical Immunology, Churchill Hospital, Oxford Radcliffe Hospitals, Oxford OX3 7LJ, UK; BerneFerryaol.com
  • Accepted 4 February 2004
  • Revised 30 January 2004

Abstract

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.

Footnotes