Proinsulin peptide-HLA class II complex on tolerogenic dendritic cells (PIpepTolDC)

The proinsulin peptide-HLA class II complex on tolerogenic dendritic cells (tolDCs) is a specialized therapeutic target and delivery platform for antigen-specific immunotherapy in Type 1 Diabetes (T1D). This complex consists of a specific proinsulin epitope, most notably the C19-A3 peptide, presented by high-risk HLA class II molecules such as HLA-DR4 (DRB1*04:01) on the surface of autologous dendritic cells (nih.gov, frontiersin.org). These dendritic cells are pharmacologically modulated (typically with Vitamin D3 and dexamethasone) to adopt a tolerogenic phenotype characterized by low costimulatory molecule expression and high inhibitory ligand density. When this complex is recognized by proinsulin-specific CD4+ T-cell receptors (TCRs), it redirects the immune response from inflammation to tolerance by inducing the differentiation of IL-10-producing regulatory T cells (Tregs) and promoting the anergy or deletion of autoreactive effector T cells (nih.gov, lancet.com). Clinical trials, such as the Phase 1 study at Leiden University Medical Center, have demonstrated that intradermal injection of these proinsulin-loaded tolDCs is safe and can induce a durable decline in autoimmune responses to proinsulin for up to three years (nih.gov). This approach aims to preserve remaining pancreatic beta-cell function by establishing 'infectious tolerance' and 'linked suppression' within the pancreatic environment.

Other names

Proinsulin-loaded tolDCstolDC-PIProinsulin-peptide-pulsed tolerogenic dendritic cellsC19-A3-loaded tolerogenic dendritic cellsProinsulin-HLA-II-tolDC complex

Induction of antigen-specific regulatory T cells (Tregs) and suppression or deletion of autoreactive CD4+ and CD8+ T cells through the presentation of proinsulin epitopes in a non-inflammatory, tolerogenic context.