T-cell receptor specific for islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) peptide (TCR-IGRP)

The T-cell receptor (TCR) specific for the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) peptide is a critical mediator of pancreatic beta-cell destruction in type 1 diabetes (T1D). IGRP is a major autoantigen expressed primarily in the islets of Langerhans, and its peptides are presented by MHC class I and II molecules to autoreactive T-cells. In the pathogenesis of T1D, CD8+ T-cells expressing TCRs that recognize IGRP peptides—most notably the IGRP 265–273 sequence in humans—selectively target and destroy insulin-producing cells. This TCR population is highly prevalent in the pancreatic infiltrates of diabetic patients and serves as a major focal point for the development of antigen-specific immunotherapies. Therapeutic strategies targeting these specific TCRs aim to induce immune tolerance rather than broad immunosuppression. Investigational drugs, such as peptide-MHC (pMHC) nanoparticles (e.g., Navacims), are designed to bind directly to IGRP-specific TCRs to reprogram pathogenic T-cells into regulatory phenotypes or induce clonal anergy. Other approaches include nanoparticle-delivered recombinant IGRP (e.g., CNP-103) to retrain the immune system through antigen-presenting cells. Monitoring the frequency and activation status of IGRP-specific T-cells is a key biomarker used in clinical trials to evaluate disease progression and the efficacy of tolerogenic treatments.

Other names

IGRP-specific T-cell receptorIGRP-reactive T-cell receptorG6PC2-specific T-cell receptorNY8.3-like T-cell receptor

Antigen-specific immune tolerance induction, T-cell anergy induction, and regulatory T-cell reprogramming