Binding of human thyrotropin receptor peptides to a Graves' disease-predisposing human leukocyte antigen class II molecule

There are many reports that Graves' disease (GD) is associated with certain human leukocyte antigen (HLA) molecules, in particular DR3. Here we examined the characteristics of binding of human TSH receptor (TSHR) peptides to this disease-associated HLA class II molecule. DR3 molecules bind TSHR immunodominant peptide epitopes with intermediate affinity. On the contrary, DR3 binds non-immunogenic peptides either with poor affinity or not at all, with one exceptional peptide that has extremely high affinity. These results suggest that susceptibility to GD associated with inheritance of a specific KLA class II gene is due to the influence of the HLA molecule-TSHR peptide complex on the T cell repertoire.