Gliadin T Cell Epitope Selection by Tissue Transglutaminase in Celiac Disease

@article{Fleckenstein2002GliadinTC,
  title={Gliadin T Cell Epitope Selection by Tissue Transglutaminase in Celiac Disease},
  author={Burkhard T. Fleckenstein and {\O}yvind Molberg and Shuo-Wang Qiao and Dietmar G. Schmid and Florian von der Mülbe and Katja Elgst{\o}en and Günther Jung and Ludvig M. Sollid},
  journal={The Journal of Biological Chemistry},
  year={2002},
  volume={277},
  pages={34109 - 34116}
}
Tissue transglutaminase (TG2) can modify proteins by transamidation or deamidation of specific glutamine residues. TG2 has a major role in the pathogenesis of celiac disease as it is both the target of disease-specific autoantibodies and generates deamidated gliadin peptides that are recognized by CD4+, DQ2-restricted T cells from the celiac lesions. Capillary electrophoresis with fluorescence-labeled gliadin peptides was used to separate and quantify deamidated and transamidated products. In a… 

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The characterization of complexes between TG2 and two immunodominant gliadin peptides and lysine residues in TG2 that act as acyl acceptors are reported, relevant to the understanding of how antibodies to TG2 are formed in celiac disease.

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Interestingly, those epitopes that were represented by intact forms were frequently recognized by T cells in celiac disease patients, whereas those that were present in truncated versions were infrequently recognized.

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The enzyme transglutaminase 2 (TG2) is deeply implicated in the development of celiac disease, an inflammatory disorder of the small intestine occurring in genetically susceptible individuals when

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

Several DQ2-restricted T-cell epitopes exist in gliadin that are located in regions rich in proline, which likely reflects epitope selection at the levels of digestive and antigen-presenting cell processing, transglutaminase-mediated deamidation, and/or peptide binding to D Q2.

Deamidated gliadin peptides as targets for celiac disease-specific antibodies.

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The Preferred Substrates for Transglutaminase 2 in a Complex Wheat Gluten Digest Are Peptide Fragments Harboring Celiac Disease T-Cell Epitopes

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Tissue Transglutaminase-Mediated Formation and Cleavage of Histamine-Gliadin Complexes: Biological Effects and Implications for Celiac Disease1

It is reported that histamine is an excellent substrate for TG2, and it can be efficiently conjugated to gluten peptides through TG2-mediated transamidation, and TG2 is able to hydrolyze the peptide-histamine conjugates when the concentrations of substrates are lowered, thereby releasing deamidated gluten peptes that are stimulatory to T cells.

Anti-type 2 transglutaminase antibodies as modulators of type 2 transglutaminase functions: a possible pathological role in celiac disease

An overview about the genesis of auto-antibodies to TG2, their specificity, their modulating ability toward TG2 enzymatic or non-enzymatic activities and their biological effects exerted by interacting with extracellular TG2 or with cell-surface TG2 is reported.
...

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