Glutamate decarboxylase 65-specific T-cell receptor (GAD65-specific TCR) (GAD65-specific TCR)

Glutamate decarboxylase 65-specific T-cell receptors (GAD65-specific TCRs) are specialized protein complexes on T-lymphocytes that recognize peptides from the GAD65 enzyme (encoded by the GAD2 gene) when presented by Major Histocompatibility Complex (MHC) molecules, particularly HLA-DR4 (PMID: 14633806). GAD65 is a primary autoantigen in Type 1 Diabetes (T1D) and Stiff-Person Syndrome, where it triggers an autoimmune response leading to the destruction of pancreatic beta cells or neurological dysfunction (PMID: 21903792). These TCRs are the primary mediators of the pathogenic cellular immune response in T1D, making them high-priority targets for antigen-specific immunotherapies. Current therapeutic strategies include the use of GAD65-based vaccines, such as GAD-alum (Diamyd), which aim to induce immune tolerance and preserve endogenous insulin production (PMID: 21714644). Additionally, researchers are exploring the engineering of regulatory T-cells (Tregs) with GAD65-specific TCRs to provide localized immunosuppression within the pancreatic environment (PMID: 33106333). Monitoring the frequency of T-cells expressing these receptors serves as a critical biomarker for disease progression and therapeutic efficacy in clinical trials.

Other names

GAD2-specific T-cell receptorGAD-65 TCRGlutamate decarboxylase 2-specific T-cell receptorGAD65-reactive T-cell receptor

Antigen-specific immune modulation through the induction of peripheral tolerance, expansion of regulatory T-cells, or desensitization of autoreactive T-lymphocytes.