T cell receptor recognizing proinsulin C19-A3–HLA-DRB1*04:01 complexes (TCR-PI-C19-A3)

The T cell receptor (TCR) recognizing the proinsulin C19-A3–HLA class II complex is a pivotal mediator in the autoimmune pathogenesis of Type 1 Diabetes (T1D). The C19-A3 peptide is an 18-amino acid epitope derived from the junction of the proinsulin C-peptide and A-chain, which is naturally processed and presented by the HLA-DR4 (specifically DRB1*04:01) MHC class II molecule (1.2.1, 1.2.2). In genetically susceptible individuals, autoreactive T cells expressing these TCRs target and destroy insulin-producing pancreatic beta cells. Therapeutic interventions, such as the MonoPepT1De and MultiPepT1De trials, utilize the C19-A3 peptide as an antigen-specific immunotherapy to 're-educate' the immune system (1.2.1, 1.3.3). By presenting this specific epitope in a non-inflammatory context, these therapies aim to induce regulatory T cells and anti-inflammatory cytokine production, thereby preserving residual beta-cell function and slowing disease progression (1.2.4, 1.3.2).

Other names

Proinsulin C19-A3-specific T cell receptorHLA-DR4-restricted proinsulin TCRTCR recognizing PI C19-A3/HLA-DR4C19-A3-specific T-cell receptor

Antigen-specific immunotherapy (ASI) designed to induce immune tolerance by promoting the expansion of regulatory T cells (Tregs) and the secretion of anti-inflammatory cytokines like IL-10, while dampening the activity of autoreactive effector T cells (1.2.1, 1.3.2).