Analysis of the binding of gluten T-cell epitopes to various human leukocyte antigen class II molecules.
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.
Bergseng
Elin
E
Centre for Immune Regulation and Institute of Immunology, Rikshospitalet University Hospital, N-0027 Oslo, Norway. elin.bergseng@rr-research.no <elin.bergseng@rr-research.no>
Sidney
John
J
Sette
Alessandro
A
Sollid
Ludvig M
LM
D017951:Antigen Presentation / Q000276:immunology; D001665:Binding Sites; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002446:Celiac Disease / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005983:Glutens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006681:HLA-D Antigens / Q000276:immunology* / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011869:Radioligand Assay
D018984:Epitopes, T-Lymphocyte; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D010446:Peptide Fragments; D005983:Glutens