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T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase.
- Source :
-
European journal of immunology [Eur J Immunol] 2001 May; Vol. 31 (5), pp. 1317-23. - Publication Year :
- 2001
-
Abstract
- Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T cell responses to ingested wheat gliadins. Initial studies used gliadin that had been subjected to non-enzymatic deamidation during pepsin/trypsin digestion to enrich for the gliadin-specific T cells in small intestinal celiac biopsies. These T cells recognized synthetic gliadin peptides only after their deamidation in vitro by purified tissue transglutaminase (tTG). However, as these studies used a deamidated antigen for re-stimulation prior to testing for antigen specificity, this raised the possibility that T cells specific for native epitopes had not been expanded in vitro and had thus been overlooked. To address this possibility and to look for more direct evidence that endogenous tTG mediates deamidation of gluten in the celiac lesions, we have here used a minimally deamidated chymotrypsin-digest of gliadin to challenge biopsies and then investigated the specificity of the T cell lines derived from them. Interestingly, these T cell lines only barely responded to the chymotrypsin-digested gliadins, but efficiently recognized the in vitro tTG-treated variants of the same gliadins. Moreover, the addition of a tTG-inhibitor during the gliadin challenge often resulted in T cell lines with abolished or reduced responses to deamidated gliadin. These data demonstrate that DQ2-restricted T cells within adult celiac lesions predominantly recognize deamidated gliadin epitopes that are formed in situ by endogenous tTG.
- Subjects :
- Antigen-Presenting Cells immunology
Biopsy
Celiac Disease enzymology
Celiac Disease pathology
Cells, Cultured
Chymotrypsin metabolism
Cystamine pharmacology
Epitopes, T-Lymphocyte chemistry
Gliadin chemistry
Gliadin metabolism
Humans
Intestines immunology
Lymphocyte Activation
T-Lymphocytes cytology
Transglutaminases antagonists & inhibitors
Amides metabolism
Celiac Disease immunology
Epitopes, T-Lymphocyte immunology
Epitopes, T-Lymphocyte metabolism
Gliadin immunology
T-Lymphocytes immunology
Transglutaminases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 31
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 11465088
- Full Text :
- https://doi.org/10.1002/1521-4141(200105)31:5<1317::AID-IMMU1317>3.0.CO;2-I