Basic–Alimentary TractCeliac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues☆,☆☆,★
Section snippets
Subjects
Nine Norwegian adult patients with celiac disease were included in the study, which was approved by the regional ethical committee. Patients CD411 and CD467 were untreated, whereas patients CD370, CD380, CD423, CD429, CD430, CD432, and CD450 were on a gluten-free diet. All subjects expressed the disease-associated DQ2 molecule encoded by DQA1*05/DQB1*02 alleles.
Amplification, cloning, and production of recombinant gliadins
By polymerase chain reaction amplification of genomic DNA isolated from the wheat strain Mjølner using γ-gliadin specific primers,11 a
Identification of 3 new DQ2-restricted T-cell epitopes in a recombinant γ-gliadin
Five individual recombinant γ-gliadins, which all contained the previously identified DQ2-γ-I and DQ2-γ-II epitopes (Table 1), were expressed in E. coli. To identify new epitopes present in the recombinant γ-gliadins, we chose a T-cell line (TCL) from patient CD411 (TCL 411E) that responded to all the tTG-treated recombinant gliadin proteins (γ-1 to γ-5) but not to the DQ2-γ-I and DQ2-γ-II epitopes. TCCs made from this TCL were used to identify positive fractions following purification of a
Discussion
An understanding of which T-cell epitopes are recognized in celiac disease and the processes leading to their selection should identify potential therapeutic targets for this disease and shed light onto the mechanisms responsible for the observed associations between HLA and disease. We previously identified 2 overlapping DQ2-restricted intestinal T-cell epitopes in α-gliadin that both contain multiple proline residues, and both require deamidation by tTG.7 Although these 2 α-gliadin epitopes
Acknowledgements
The authors thank Marie Kongshaug Johannesen, Eva Boretti, and Nicole Sessler for excellent technical assistance as well as the patients with celiac disease who donated biological material for this study.
References (24)
Current concepts of celiac disease pathogenesis
Gastroenterology
(2000)- et al.
T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8
Hum Immunol
(1994) - et al.
Nucleotide sequence of a gamma-gliadin gene: comparisons with other gamma-gliadin sequences show the structure of gamma-gliadin genes and the general primary structure of gamma-gliadins
Plant Sci
(1988) Molecular basis of celiac disease
Annu Rev Immunol
(2000)- et al.
Gliadin-specific, HLA-DQ(α1*0501,β1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients
J Exp Med
(1993) - et al.
Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease
Nat Med
(1998) - et al.
Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity
J Immunol
(1998) - et al.
The intestinal T cell response to α-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase
J Exp Med
(2000) - et al.
HLA binding and T cell recognition of a tissue transglutaminase-modified gliadin epitope
Eur J Immunol
(1999) - et al.
D. Cereal proteins and coeliac disease
Identification of a gliadin T-cell epitope in coeliac disease: general importance of gliadin deamidation for intestinal T-cell recognition
Scand J Immunol
Production of a panel of recombinant gliadins for the characterisation of T cell reactivity in coeliac disease
Gut
Cited by (313)
CRISPR-mediated acceleration of wheat improvement: advances and perspectives
2023, Journal of Genetics and GenomicsEx vivo gliadin stimulation of intestinal cells
2023, Methods in Cell BiologyStructural bases of T cell antigen receptor recognition in celiac disease
2022, Current Opinion in Structural BiologyEffect of additional water supply during grain filling on protein composition and epitope characteristics of winter oats
2022, Current Research in Food ScienceEngineering wheat for gluten safe
2021, Biotechnological Strategies for the Treatment of Gluten Intolerance
- ☆
Address requests for reprints to: Ludvig M. Sollid, M.D., Institute of Immunology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway. e-mail: [email protected]; fax: (47) 230 73822.
- ☆☆
Supported by research grants from the Research Council of Norway, the European Commission (BMH4-CT98-3087, QLRT-2000-00657, QLGA-CT-2000-51218), the Norwegian Foundation for Health and Rehabilitation, and the Deutsche Forschungsgemeinschaft (SFB 510, project D4).
- ★
H.A.-H. and S.N.M. contributed equally to this study.