HLA-DR class II molecules presenting Thyroid-stimulating hormone receptor-derived epitopes (HLA-DR/TSHR-peptide complex)

HLA-DR class II molecules presenting Thyroid-stimulating hormone receptor (TSHR)-derived epitopes are critical mediators in the development of Graves' disease (GD) (PubMed: 25603471). In genetically susceptible individuals, particularly those carrying the HLA-DRB1*03:01 allele, these MHC class II molecules present specific TSHR peptide fragments to autoreactive CD4+ T cells (PubMed: 15105453). This interaction drives the activation of B cells to produce thyroid-stimulating immunoglobulins (TSI), which bind to and activate the TSHR, causing hyperthyroidism and goiter (UniProt: P16473). Therapeutic intervention targeting this complex involves antigen-specific immunotherapy, such as ATX-GD-59, which consists of soluble TSHR-derived peptides (Apitopes) (ClinicalTrials.gov: NCT02973802). These peptides are designed to bind directly to HLA-DR molecules on antigen-presenting cells in a way that promotes immunological tolerance rather than activation, potentially halting the autoimmune process without systemic immunosuppression (PubMed: 29453464).

Other names

MHC class II/TSHR peptide complexHLA-DR/TSHR epitope complexTSHR-peptide/HLA-DR complexThyroid-stimulating hormone receptor peptide-HLA-DR complexApitope-HLA-DR complex

Induction of antigen-specific T-cell tolerance through the presentation of soluble Thyroid-stimulating hormone receptor-derived peptides (Apitopes) by HLA-DR molecules in the absence of costimulatory signals, leading to T-cell anergy or the induction of regulatory T-cells (PubMed: 29453464).