T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease

Nat Struct Mol Biol. 2014 May;21(5):480-8. doi: 10.1038/nsmb.2817. Epub 2014 Apr 28.


Celiac disease is a T cell-mediated disease induced by dietary gluten, a component of which is gliadin. 95% of individuals with celiac disease carry the HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epitopes from wheat gliadin, DQ2.5-glia-α1a and DQ2.5-glia-α2. We determined the ternary structures of four distinct biased TCRs specific for those epitopes. All three TCRs specific for DQ2.5-glia-α2 docked centrally above HLA-DQ2, which together with mutagenesis and affinity measurements provided a basis for the biased TCR usage. A non-germline encoded arginine residue within the CDR3β loop acted as the lynchpin within this common docking footprint. Although the TCRs specific for DQ2.5-glia-α1a and DQ2.5-glia-α2 docked similarly, their interactions with the respective gliadin determinants differed markedly, thereby providing a basis for epitope specificity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Celiac Disease / immunology*
  • Epitopes, T-Lymphocyte / chemistry*
  • Gliadin / chemistry*
  • Gliadin / immunology
  • HLA-DQ Antigens / chemistry*
  • Humans
  • Immunogenetic Phenomena
  • Models, Molecular
  • Molecular Conformation
  • Receptors, Antigen, T-Cell / chemistry*
  • Triticum


  • Epitopes, T-Lymphocyte
  • HLA-DQ Antigens
  • Receptors, Antigen, T-Cell
  • Gliadin

Associated data

  • PDB/4OZF
  • PDB/4OZG
  • PDB/4OZH
  • PDB/4OZI