Preproinsulin 15-24 peptide–HLA-A*02:01 complex (PPI15-24–HLA-A*02:01)

The Preproinsulin 15-24 peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a primary autoantigen in Type 1 Diabetes (T1D). It comprises a 10-amino acid sequence (ALWGPDPAAA) derived from the signal peptide of preproinsulin, which is presented by the HLA-A*02:01 class I molecule (Skowera et al., 2008, J Clin Invest). This complex is recognized by autoreactive CD8+ T cells, leading to the targeted destruction of insulin-producing pancreatic beta cells (Kronenberg-Versteeg et al., 2014, Diabetes). Because HLA-A*02:01 is the most common HLA allele associated with T1D risk, this pMHC is a major focus for therapeutic intervention. Strategies include the development of TCR-like antibodies for diagnostic imaging and the creation of tolerogenic vaccines or TCR-based therapies designed to suppress or eliminate the specific T-cell clones responsible for beta-cell loss (Luce et al., 2011, J Autoimmun; Insel et al., 2015, Nat Rev Dis Primers).

Other names

Preproinsulin(15-24)/HLA-A*02:01ALWGPDPAAA/HLA-A*02:01Insulin signal peptide 15-24/HLA-A2PPI signal peptide epitope

Targeted modulation of the immune system through T-cell receptor (TCR) recognition of the peptide-MHC complex to induce tolerance or deplete autoreactive cells.