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Gut. 2004 Sep;53(9):1274-8.

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

Author information

  • 1Department of Clinical Immunology, Churchill Hospital, Oxford Radcliffe Hospitals, Oxford OX3 7LJ, UK. BerneFerry@aol.com

Abstract

BACKGROUND:

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

PMID:
15306584
PMCID:
PMC1774203
DOI:
10.1136/gut.2003.032755
[PubMed - indexed for MEDLINE]
Free PMC Article
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