Skip to main content
SpringerLink
Log in

Update 2020: nomenclature and listing of celiac disease–relevant gluten epitopes recognized by CD4+ T cells

  • Review
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Celiac disease is caused by an abnormal intestinal T cell response to cereal gluten proteins. The disease has a strong human leukocyte antigen (HLA) association, and CD4+ T cells recognizing gluten epitopes presented by disease-associated HLA-DQ allotypes are considered to be drivers of the disease. This paper provides an update of the currently known HLA-DQ restricted gluten T cell epitopes with their names and sequences.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Arentz-Hansen H, Körner R, Molberg Ø, Quarsten H, Vader W, Kooy YM, Lundin KEA, Koning F, Roepstorff P, Sollid LM, McAdam SN (2000) 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 191:603–612

    Article  CAS  Google Scholar 

  • Arentz-Hansen H, McAdam SN, Molberg Ø, Fleckenstein B, Lundin KE, Jorgensen TJ, Jung G, Roepstorff P, Sollid LM (2002) Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues. Gastroenterology 123:803–809

    Article  Google Scholar 

  • Arentz-Hansen H, Fleckenstein B, Molberg Ø, Scott H, Koning F, Jung G, Roepstorff P, Lundin KE, Sollid LM (2004) The molecular basis for oat intolerance in patients with celiac disease. PLoS Med 1:e1

    Article  Google Scholar 

  • Bodd M, Kim CY, Lundin KE, Sollid LM (2012) T-cell response to gluten in patients with HLA-DQ2.2 reveals requirement of peptide-MHC stability in celiac disease. Gastroenterology 142:552–561

    Article  CAS  Google Scholar 

  • Camarca A, Auricchio R, Picascia S, Fierro O, Maglio M, Miele E, Malamisura B, Greco L, Troncone R, Gianfrani C (2017) Gliadin-reactive T cells in Italian children from preventCD cohort at high risk of celiac disease. Pediatr Allergy Immunol 28:362–369

    Article  Google Scholar 

  • Dørum S, Bodd M, Fallang LE, Bergseng E, Christophersen A, Johannesen MK, Qiao SW, Stamnaes J, de Souza GA, Sollid LM (2014) HLA-DQ molecules as affinity matrix for identification of gluten T cell epitopes. J Immunol 193:4497–4506

    Article  Google Scholar 

  • Gil-Humanes J, Piston F, Tollefsen S, Sollid LM, Barro F (2010) Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference. Proc Natl Acad Sci U S A 107:17023–17028

    Article  CAS  Google Scholar 

  • Hardy MY, Girardin A, Pizzey C, Cameron DJ, Watson KA, Picascia S, Auricchio R, Greco L, Gianfrani C, La Gruta NL, Anderson RP, Tye-Din JA (2015a) Consistency in polyclonal T-cell responses to gluten between children and adults with celiac disease. Gastroenterology 149:1541–1552 e2

    Article  CAS  Google Scholar 

  • Hardy MY, Tye-Din JA, Stewart JA, Schmitz F, Dudek NL, Hanchapola I, Purcell AW, Anderson RP (2015b) Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides. J Autoimmun 56:56–65

    Article  CAS  Google Scholar 

  • International Wheat Genome Sequencing CI (2018) Shifting the limits in wheat research and breeding using a fully annotated reference genome. Science 361

  • Jouanin A, Schaart JG, Boyd LA, Cockram J, Leigh FJ, Bates R, Wallington EJ, Visser RGF, Smulders MJM (2019) Outlook for coeliac disease patients: towards bread wheat with hypoimmunogenic gluten by gene editing of α- and γ-gliadin gene families. BMC Plant Biol 19:333

    Article  Google Scholar 

  • Kooy-Winkelaar Y, van Lummel M, Moustakas AK, Schweizer J, Mearin ML, Mulder CJ, Roep BO, Drijfhout JW, Papadopoulos G, van Bergen J, Koning F (2011) Gluten-specific T cells cross-react between HLA-DQ8 and the HLA-DQ2α/DQβ transdimer. J Immunol 187:5123–5129

    Article  CAS  Google Scholar 

  • Petersen J, Kooy-Winkelaar Y, Loh KL, Tran M, van Bergen J, Koning F, Rossjohn J, Reid HH (2016) Diverse T cell receptor gene usage in HLA-DQ8-associated celiac disease converges into a consensus binding solution. Structure 24:1643–1657

    Article  CAS  Google Scholar 

  • Qiao SW, Sollid LM (2019) Two novel HLA-DQ2.5-restricted gluten T-cell epitopes in the DQ2.5-glia-γ4 epitope family. Immunogenetics https://doi.org/10.1007/s00251-019-01138-5

    Article  CAS  Google Scholar 

  • Qiao SW, Bergseng E, Molberg Ø, Jung G, Fleckenstein B, Sollid LM (2005) Refining the rules of gliadin T cell epitope binding to the disease-associated DQ2 molecule in celiac disease: importance of proline spacing and glutamine deamidation. J Immunol 175:254–261

    Article  CAS  Google Scholar 

  • Ráki M, Dahal-Koirala S, Yu H, Korponay-Szabo IR, Gyimesi J, Castillejo G, Jahnsen J, Qiao SW, Sollid LM (2017) Similar responses of intestinal T cells from untreated children and adults with celiac disease to deamidated gluten epitopes. Gastroenterology 153:787–798 e4

    Article  Google Scholar 

  • Sanchez-Leon S, Gil-Humanes J, Ozuna CV, Gimenez MJ, Sousa C, Voytas DF, Barro F (2018) Low-gluten, nontransgenic wheat engineered with CRISPR/Cas9. Plant Biotechnol J 16:902–910

    Article  CAS  Google Scholar 

  • Sjöström H, Lundin KEA, Molberg Ø, Körner R, McAdam SN, Anthonsen D, Quarsten H, Noren O, Roepstorff P, Thorsby E, Sollid LM (1998) Identification of a gliadin T-cell epitope in coeliac disease: general importance of gliadin deamidation for intestinal T-cell recognition. Scand J Immunol 48:111–115

    Article  Google Scholar 

  • Sollid LM, Qiao SW, Anderson RP, Gianfrani C, Koning F (2012) Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics 64:455–460

    Article  Google Scholar 

  • Stepniak D, Vader LW, Kooy Y, van Veelen PA, Moustakas A, Papandreou NA, Eliopoulos E, Drijfhout JW, Papadopoulos GK, Koning F (2005) T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1. Immunogenetics 57:8–15

    Article  CAS  Google Scholar 

  • Tollefsen S, Arentz-Hansen H, Fleckenstein B, Molberg Ø, Ráki M, Kwok WW, Jung G, Lundin KE, Sollid LM (2006) HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease. J Clin Invest 116:2226–2236

    Article  CAS  Google Scholar 

  • Tye-Din JA, Stewart JA, Dromey JA, Beissbarth T, van Heel DA, Tatham A, Henderson K, Mannering SI, Gianfrani C, Jewell DP, Hill AV, McCluskey J, Rossjohn J, Anderson RP (2010) Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci Transl Med 2:41ra51

    Article  Google Scholar 

  • Vader W, Kooy Y, van Veelen P, de Ru A, Harris D, Benckhuijsen W, Pena S, Mearin L, Drijfhout JW, Koning F (2002) The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. Gastroenterology 122:1729–1737

    Article  CAS  Google Scholar 

  • Vader LW, Stepniak DT, Bunnik EM, Kooy YM, de Haan W, Drijfhout JW, van Veelen PA, Koning F (2003) Characterization of cereal toxicity for celiac disease patients based on protein homology in grains. Gastroenterology 125:1105–1113

    Article  CAS  Google Scholar 

  • van de Wal Y, Kooy YM, van Veelen PA, Pena SA, Mearin LM, Molberg Ø, Lundin KEA, Sollid LM, Mutis T, Benckhuijsen WE, Drijfhout JW, Koning F (1998) Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin. Proc Natl Acad Sci U S A 95:10050–10054

    Article  Google Scholar 

  • van de Wal Y, Kooy YM, van Veelen P, Vader W, August SA, Drijfhout JW, Pena SA, Koning F (1999) Glutenin is involved in the gluten-driven mucosal T cell response. Eur J Immunol 29:3133–3139

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. KG Jebsen Coeliac Disease Research Centre and Department of Immunology, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway

    Ludvig M. Sollid & Shuo-Wang Qiao

  2. Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    Jason A. Tye-Din & Robert P. Anderson

  3. Institute of Biochemistry and Cell Biology, National Research Council of Italy, Naples, Italy

    Carmen Gianfrani

  4. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

    Frits Koning

Authors
  1. Ludvig M. Sollid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jason A. Tye-Din
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuo-Wang Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert P. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carmen Gianfrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Frits Koning
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ludvig M. Sollid.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on “Nomenclature, databases and bioinformatics in Immunogenetics”.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sollid, L.M., Tye-Din, J.A., Qiao, SW. et al. Update 2020: nomenclature and listing of celiac disease–relevant gluten epitopes recognized by CD4+ T cells. Immunogenetics 72, 85–88 (2020). https://doi.org/10.1007/s00251-019-01141-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-019-01141-w

Keywords

Search

Navigation