Analysis of the binding of gluten T-cell epitopes to various human leukocyte antigen class II molecules

Hum Immunol. 2008 Feb;69(2):94-100. doi: 10.1016/j.humimm.2008.01.002. Epub 2008 Feb 8.

Abstract

Celiac disease is a prevalent disorder of the small intestine that is caused by an inflammatory reaction to dietary gluten in genetically susceptible individuals. More than 90% of patients express the HLA-DQ2 molecule, whereas DQ8 is carried by most of the remaining patients. DQ2- and DQ8-mediated presentation of gluten peptides to CD4+ T cells is a key event in the pathogenesis of the disease. The association of celiac disease with these human leukocyte antigen (HLA) molecules is explained by a preferential binding of gluten peptides to these HLA molecules, although the actual data on this in the literature are scarce. The objective of this study was to test this hypothesis. A panel of peptides representing DQ2-restricted gluten T-cell epitopes was tested for binding to various HLA class II molecules using various experimental approaches. The results demonstrate that the gluten T-cell epitopes mainly bind to the DQ2 molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology
  • Binding Sites
  • Binding, Competitive
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Celiac Disease / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / metabolism
  • Genetic Predisposition to Disease
  • Glutens / chemistry
  • Glutens / immunology*
  • Glutens / metabolism
  • HLA-D Antigens / immunology*
  • HLA-D Antigens / metabolism
  • HLA-DQ Antigens / immunology
  • HLA-DQ Antigens / metabolism
  • Humans
  • Hydrogen Bonding
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Radioligand Assay

Substances

  • Epitopes, T-Lymphocyte
  • HLA-D Antigens
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen
  • Peptide Fragments
  • Glutens