ArticleProceedings of the National Academy of Sciences of the United States of America2012
A single conformational transglutaminase 2 epitope contributed by three domains is critical for celiac antibody binding and effects.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 65 citations in OpenAlex.
- Changes in Non-Deamidated versus Deamidated Epitope Targeting and Disease Prediction during the Antibody Response to Gliadin and Transglutaminase of Infants at Risk for Celiac Disease.International journal of molecular sciences · 2022Trial
- Intestinal-mucosa anti-transglutaminase antibody assays to test for genetic gluten intolerance.Cellular & molecular immunology · 2014Trial
- Transcriptomics and eQTLs reveal inflammatory heterogeneity in the duodenal lining in coeliac disease.Genes and immunity · 2025Article
- Development of Cell-Assembled Human Endomysial-Type Biomatrix Substrate for the Detection of Celiac Disease Autoantibodies.International journal of molecular sciences · 2025Article
- Structures of Human Transglutaminase 2: Finding Clues for Interference in Cross-linking Mediated Activity.International journal of molecular sciences · 2020Review
- Transglutaminase 2 and Transglutaminase 2 Autoantibodies in Celiac Disease: a Review.Clinical reviews in allergy & immunology · 2019Review
- Gluten-Induced Extra-Intestinal Manifestations in Potential Celiac Disease-Celiac Trait.Nutrients · 2019Review
- Anti-type 2 transglutaminase antibodies as modulators of type 2 transglutaminase functions: a possible pathological role in celiac disease.Cellular and molecular life sciences : CMLS · 2018Review
- Article
- Strong Clonal Relatedness between Serum and Gut IgA despite Different Plasma Cell Origins.Cell reports · 2017Article
- Transglutaminase 2 in human diseases.BioMedicine · 2017Article
- Article
- Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP).ACS central science · 2016Article
- Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease.The Journal of biological chemistry · 2015Article
- Physiological, pathological, and structural implications of non-enzymatic protein-protein interactions of the multifunctional human transglutaminase 2.Cellular and molecular life sciences : CMLS · 2015Review
- Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Fingertip rapid point-of-care test in adult case-finding in coeliac disease.BMC gastroenterology · 2013Article
- Transglutaminase 2-specific autoantibodies in celiac disease target clustered, N-terminal epitopes not displayed on the surface of cells.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Article
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multifunctional, protein cross-linking transglutaminase 2 (TG2) is the main autoantigen in celiac disease, an autoimmune disorder with defined etiology. Glutamine-rich gliadin peptides from ingested cereals, after their deamidation by TG2, induce T-lymphocyte activation accompanied by autoantibody production against TG2 in 1-2% of the population. The pathogenic role and exact binding properties of these antibodies to TG2 are still unclear. Here we show that antibodies from different celiac patients target the same conformational TG2 epitope formed by spatially close amino acids of adjacent domains. Glu153 and 154 on the first alpha-helix of the core domain and Arg19 on first alpha-helix of the N-terminal domain determine the celiac epitope that is accessible both in the closed and open conformation of TG2 and dependent on the relative position of these helices. Met659 on the C-terminal domain also can cooperate in antibody binding. This composite epitope is disease-specific, recognized by antibodies derived from celiac tissues and associated with biological effects when passively transferred from celiac mothers into their newborns. These findings suggest that celiac antibodies are produced in a surface-specific way for which certain homology of the central glutamic acid residues of the TG2 epitope with deamidated gliadin peptides could be a structural basis. Monoclonal mouse antibodies with partially overlapping epitope specificity released celiac antibodies from patient tissues and antagonized their harmful effects in cell culture experiments. Such antibodies or similar specific competitors will be useful in further functional studies and in exploring whether interference with celiac antibody actions leads to therapeutic benefits.
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