HLA-DRB1*0401-restricted proinsulin C19-A3-specific T-cell receptor (TCR-PI C19-A3/DR4)

The HLA-DRB1*0401-restricted proinsulin C19-A3-specific T-cell receptor (TCR) is a specialized immune receptor that plays a central role in the autoimmune destruction of pancreatic beta cells in Type 1 Diabetes (T1D). This TCR recognizes the C19-A3 peptide, an 18-amino acid fragment of proinsulin, when it is presented by the MHC class II molecule HLA-DRB1*0401 (DR4), a major genetic risk factor for the disease (Durinovic-Belló et al., 2006; Alhadj Ali et al., 2017). In T1D patients, this interaction typically activates proinflammatory CD4+ effector T cells, whereas in healthy individuals, it may be associated with regulatory T cell (Treg) responses (Durinovic-Belló et al., 2006; Thrower et al., 2009). Therapeutic strategies, such as peptide immunotherapy (PIT), utilize the C19-A3 peptide to redirect the immune system toward tolerance by inducing the expansion of IL-10-producing Tr1 cells and Foxp3+ Tregs (Alhadj Ali et al., 2017; Kroger et al., 2018). Clinical trials have demonstrated that this approach is safe and can help preserve residual insulin production, as measured by C-peptide levels, in newly diagnosed patients (Alhadj Ali et al., 2017; BioWorld, 2017). By specifically targeting the proinsulin-reactive T-cell population, these therapies aim to halt disease progression without the risks associated with broad systemic immunosuppression (Alhadj Ali et al., 2017; Kroger et al., 2018).

Other names

Proinsulin C19-A3-specific TCRHLA-DR4-restricted proinsulin TCRC19-A3-specific T-cell receptorProinsulin peptide C19-A3-MHC complexMonoPepT1De

Induction of antigen-specific immune tolerance through the expansion of regulatory T cells (Tregs), particularly IL-10-producing Tr1 cells, and the functional inactivation or deletion of pathogenic effector T cells (Teff) recognizing the proinsulin C19-A3 epitope presented by HLA-DRB1*0401.