Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues.
OBJECTIVE
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.
Institute of Immunology and Department of Medicine, Rikshopitalet, University of Oslo, Oslo, Norway.
Helene
H
Arentz-Hansen
Stephen N
SN
McAdam
Øyvind
Ø
Molberg
Burkhard
B
Fleckenstein
Knut E A
KE
Lundin
Thomas J D
TJ
Jørgensen
Günther
G
Jung
Peter
P
Roepstorff
Ludvig M
LM
Sollid
D000595:Amino Acid Sequence / Q000235:genetics; D002446:Celiac Disease / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005903:Gliadin / Q000235:genetics* / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011392:Proline; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D011994:Recombinant Proteins; D005903:Gliadin; D011392:Proline