Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues

被引:278
作者
Arentz-Hansen, H
McAdam, SN
Molberg, O
Fleckenstein, B
Lundin, KEA
Jorgensen, TJD
Jung, G
Roepstorff, P
Sollid, LM [1 ]
机构
[1] Univ Oslo, Rikshosp, Inst Immunol, N-0027 Oslo, Norway
[2] Univ Oslo, Rikshosp, Dept Med, N-0027 Oslo, Norway
[3] Univ Tubingen, Inst Organ Chem, D-7400 Tubingen, Germany
[4] Univ So Denmark, Dept Biochem & Mol Biol, Odense, Denmark
关键词
D O I
10.1053/gast.2002.35381
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Celiac disease is a gluten-induced enteropathy that shows a strong association with HLA-DQ2 and -DQ8. Gluten-specific T cells, invariably restricted by DQ2 or DQ8, can be isolated from celiac lesions. Such gut-derived T cells have a preference for recognition of gluten that has been specifically deamidated by tissue transglutaminase. Only a few gliadin T-cell epitopes have been identified by earlier work. The aim of this study was to perform a systematic characterization of DQ2-restricted T-cell epitopes in alpha- and gamma-gliadins. Methods: Epitopes were identified by mass spectrometry analysis of peptide fragments of recombinant gliadins and by use of synthetic peptides. Results: We identified several new gamma-gliadin epitopes and an additional alpha-gliadin epitope. Interestingly, these and the previously identified epitopes are not randomly scattered across the gliadins but cluster in regions of the proteins with high content of proline residues. Conclusions: Several DQ2-restricted T-cell epitopes exist in gliadin that are located in regions rich in proline. This likely reflects epitope selection at the levels of digestive and antigen-presenting cell processing, transglutaminase-mediated deamidation, and/or peptide binding to DQ2.
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收藏
页码:803 / 809
页数:7
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