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) consisting of a 10-amino acid fragment from the preproinsulin signal peptide (residues 15-24: ALWGPDPAAA) bound to the HLA-A*02:01 molecule (Skowera et al., 2008). This complex is a critical autoantigen in the pathogenesis of Type 1 Diabetes (T1D), where it is presented on the surface of pancreatic beta cells and recognized by autoreactive CD8+ T cells (Kronenberg-Versteeg et al., 2016). The destruction of these beta cells by the immune system leads to the loss of insulin production, the hallmark of T1D. As a therapeutic target, the complex is being utilized to develop precision immunotherapies, such as TCR-like antibodies and TCR-engineered T cells, which aim to specifically target or modulate the pathogenic T-cell response (Shchelykalnov et al., 2021). These approaches are designed to provide a highly specific treatment that avoids the side effects of broad immunosuppression. Monitoring the frequency of T cells reactive to this complex also serves as a potential biomarker for disease progression and therapeutic efficacy (Skowera et al., 2008). The high prevalence of the HLA-A*02:01 allele in T1D patients makes this complex a particularly attractive target for population-wide therapeutic strategies.

Other names

PPI 15-24/HLA-A*02:01ALWGPDPAAA-HLA-A*02:01 complexPreproinsulin signal peptide-MHC complexPPI(15-24)-MHC class I complex

Targeting of the peptide-MHC complex by engineered T-cell receptors or antibodies to modulate or deplete autoreactive CD8+ T cells.