A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease

Immunity. 2007 Jul;27(1):23-34. doi: 10.1016/j.immuni.2007.05.015. Epub 2007 Jul 12.


The risk of celiac disease is strongly associated with human leukocyte antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the pathogenesis of HLA-DQ2-mediated celiac disease is established, the underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac pathology were indeed HLA DQ8 restricted and that multiple, mostly deamidated peptides derived from protease-sensitive sites of gliadin were recognized. This pattern of reactivity contrasted with the more absolute deamidation dependence and relative protease resistance of the dominant gliadin peptide in DQ2-mediated disease. We provided a structural basis for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The data established that the molecular mechanisms underlying HLA-DQ8-mediated celiac disease differed markedly from the HLA-DQ2-mediated form of the disease. Accordingly, nondietary therapeutic interventions in celiac disease might need to be tailored to the genotype of the individual.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / metabolism
  • Amino Acid Sequence
  • Antigen Presentation / immunology
  • Celiac Disease / immunology*
  • Celiac Disease / metabolism*
  • Cells, Cultured
  • Clone Cells
  • Crystallography, X-Ray
  • Gliadin / immunology
  • Gliadin / metabolism
  • Gliadin / ultrastructure
  • HLA-DQ Antigens / chemistry*
  • HLA-DQ Antigens / physiology*
  • HLA-DQ Antigens / ultrastructure
  • Humans
  • Hydrolysis
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Peptide Hydrolases / chemistry
  • Structure-Activity Relationship
  • Th1 Cells / immunology
  • Th1 Cells / metabolism


  • Amides
  • HLA-DQ Antigens
  • HLA-DQ8 antigen
  • Peptide Fragments
  • Gliadin
  • Peptide Hydrolases

Associated data

  • PDB/2NNA