Islet-specific glucose-6-phosphatase catalytic subunit-related protein peptide 305-324–HLA-DRB1*04:01 complex (IGRP305-MHC)

The IGRP305 peptide–MHC complex is a specific molecular target in Type 1 Diabetes (T1D) consisting of a peptide fragment from the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), specifically residues 305–324, presented by the MHC class II molecule HLA-DRB1*04:01 [1.2.1]. This complex is primarily expressed on the surface of professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, within the pancreatic islets and associated lymphoid tissues [1.2.1, 1.4.3]. In the pathogenesis of T1D, the recognition of this complex by autoreactive CD4+ effector T cells triggers an inflammatory cascade that leads to the destruction of insulin-producing beta cells [1.2.1, 1.4.4]. Modern therapeutic strategies, such as the engineered regulatory T cell (Treg) therapy GNTI-122, target this complex to redirect the immune system toward tolerance [1.2.2]. By specifically binding to the IGRP305-MHC complex, these therapeutic Tregs are activated to suppress local autoimmune activity and protect the remaining beta cell mass [1.2.3]. This interaction facilitates bystander suppression, where the activated Tregs release inhibitory cytokines that dampen the activity of other nearby autoreactive T cells regardless of their specific antigen [1.2.1, 1.2.4]. This approach offers a precision method for treating T1D by restoring immune homeostasis in the pancreas without the risks associated with systemic immunosuppression [1.2.1, 1.3.4].

Other names

IGRP305-324/HLA-DRB1*04:01 complexIGRP305-324/DR4 complexIGRP305-MHC II complexG6PC2(305-324)/HLA-DR4IGRP305 peptide–MHC complex

Antigen-specific activation of engineered regulatory T cells (Tregs) that recognize the pMHC complex on antigen-presenting cells, leading to localized suppression of effector T cells and induction of immune tolerance.