TITLE

An immunodominant DQ8 restricted gliadin peptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients

AUTHOR(S)
Mazzarella, G.; Maglio, M.; Paparo, F.; Nardone, G.; Stefanile, R.; Greco, L.; van de Wal, Y.; Kooy, Y.; Koning, F.; Auricchio, S.; Troncone, R.
PUB. DATE
January 2003
SOURCE
Gut;Jan2003, Vol. 52 Issue 1, p57
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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[sup +] and lamina propria total CD25[sup +] and CD3[sup +]CD25[sup +] 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[sup +] cells, lamina propria total CD25[sup +], and CD3[sup +]CD25[sup +] 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.
ACCESSION #
9758406

 

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