Article Text
Abstract
Background: Studies on intestinal T cell clones from the mucosa of patients with coeliac disease have led to the identification of immunogenic gliadin epitopes. One is HLA-DQ8 restricted, its recognition by T cells being increased by introduction of negatively charged residues operated by tissue transglutaminase.
Aim: To test HLA-DQ8 restricted epitope in both native (QYPSGQGSFQPSQQNPQA) and deamidated (QYPSGEGSFQPSQENPQA) forms in an organ culture system of treated coeliac mucosa from HLA-DQ8 positive and HLA-DQ8 negative patients.
Patients and methods: Jejunal biopsies obtained from 10 patients with coeliac disease (six HLA-DQ8 positive and four HLA-DQ8 negative) were cultured in vitro with a peptic-tryptic digest (PT) of gliadin, or with the native (peptide A) or deamidated (peptide B) peptide. Intraepithelial CD3+ and lamina propria total CD25+ and CD3+CD25+ cells were counted, lamina propria intercellular adhesion molecule 1 (ICAM-1) expression was evaluated, as well as that of Fas molecules on epithelial cells.
Results: In HLA-DQ8 positive, but not in HLA-DQ8 negative, coeliacs the density of intraepithelial CD3+ cells, lamina propria total CD25+, and CD3+CD25+ cells, as well as expression of ICAM-1 and Fas molecules were significantly increased in biopsies cultured with PT, peptide A, or peptide B compared with biopsies cultured in medium alone.
Conclusion: These data show that the DQ8 restricted gliadin peptide is immunogenic only in the intestinal mucosa of HLA-DQ8 positive coeliac patients in both native and deamidated forms.
- coeliac disease
- gliadin peptides
- HLA restriction
- organ culture
- mucosal immunity
- Fas
- CD, coeliac disease
- LPMNC, lamina propria mononuclear cells
- PT, peptic-tryptic digest
- TBS, Tris buffered saline
- PAP, peroxidase-antiperoxidase
- APAAP, alkaline phosphatase/antialkaline phosphatase
- PBS, phosphate buffered saline
- ICAM-1, intercellular adhesion molecule 1
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