Islet-specific glucose-6-phosphatase catalytic subunit-related protein peptide–MHC complex (IGRP-pMHC)

The Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) peptide–MHC complex is a pivotal molecular target in the study and treatment of Type 1 Diabetes (T1D). IGRP is an endoplasmic reticulum-resident protein highly expressed in pancreatic beta cells, and its degradation products are presented as peptides on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (UniProt Q9NQR9). These complexes are primary targets for autoreactive CD8+ T cells, which recognize them and subsequently mediate the destruction of insulin-producing cells (PubMed: 15107844). In therapeutic development, synthetic versions of these pMHC complexes are being engineered into nanoparticle platforms, such as Navacims, to reprogram the immune system. These therapies aim to bind specifically to the T-cell receptors of pathogenic cells to induce their conversion into regulatory T cells or trigger their exhaustion, thereby halting the autoimmune attack without compromising general immunity (PubMed: 20383155).

Other names

IGRP peptide-HLA complexG6PC2 peptide-MHC complexIslet-specific glucose-6-phosphatase catalytic subunit-related protein peptide-major histocompatibility complexIGRP-pMHC class I complex

Induction of antigen-specific immune tolerance by expanding regulatory T cells (Tregs) or depleting/anergizing autoreactive CD8+ T cells that recognize the IGRP-pMHC complex on beta cells.