T-cell receptor on autoreactive T-cells specific for proinsulin II and glutamic acid decarboxylase peptides (TCR)

T-cell receptors (TCRs) on autoreactive T-cells are the primary mediators of the autoimmune destruction of pancreatic beta cells in Type 1 Diabetes (T1D). These receptors specifically recognize peptides derived from key beta-cell autoantigens, most notably proinsulin (specifically proinsulin II in murine models) and glutamic acid decarboxylase 65 (GAD65), presented by specific MHC/HLA class II molecules (Nakayama et al., Nature 2005). The binding of these TCRs to their cognate peptide-MHC complexes triggers T-cell activation, proliferation, and the subsequent release of pro-inflammatory cytokines and cytotoxic granules. Because these T-cells are the executioners of the disease, they represent a high-value target for precision immunotherapy. Current therapeutic strategies include the use of altered peptide ligands, tolerogenic vaccines like Diamyd, and monoclonal antibodies like teplizumab to modulate or deplete these specific cell populations (Herold et al., NEJM 2019; Ludvigsson et al., NEJM 2012). The ultimate goal of targeting these TCRs is to halt the progression of T1D and preserve endogenous insulin secretion while avoiding the risks of broad systemic immunosuppression.

Other names

Autoreactive T-cell receptorProinsulin-specific TCRGAD65-specific TCRDiabetogenic T-cell receptorIns2-specific T-cell receptor

Antigen-specific immunotherapy designed to induce immune tolerance, anergy, or deletion of autoreactive T-cell clones.