Coagulation factor VIII peptide-Major Histocompatibility Complex class II complex (FVIII peptide-MHC II)

The target is a specific antigenic complex consisting of a peptide derived from the C2 domain of Coagulation factor VIII (FVIII) presented on Major Histocompatibility Complex class II (MHC II) molecules, specifically HLA-DRB1*01:01 (Mahan et al., 2017). This complex is the specific ligand for the TI-168 T-cell receptor (TCR), a human TCR cloned from a Hemophilia A patient who developed high-titer inhibitors (Kim et al., 2015). In the context of modern immunotherapy, the TI-168 TCR is utilized to engineer regulatory T cells (Tregs) to induce antigen-specific immune tolerance in Hemophilia A patients (Scott et al., 2018). When these engineered Tregs encounter the FVIII peptide-MHC II complex on antigen-presenting cells or B cells, they become activated and suppress the immune response against FVIII through the secretion of inhibitory cytokines and direct cellular interactions (Yoon et al., 2017). This therapeutic strategy is designed to prevent or eliminate the formation of neutralizing anti-FVIII antibodies, known as inhibitors, which are a major complication in the treatment of Hemophilia A (Mahan et al., 2017).

Other names

FVIII:C2 peptide-HLA-DR complexFVIII-derived peptide presented on MHCTI-168 TCR ligandFVIII 2191–2210 peptide-MHC II complex

The TI-168 TCR-engineered regulatory T cells recognize the FVIII peptide presented on MHC II, leading to the activation of the Treg and subsequent suppression of FVIII-specific B cells and T helper cells through the secretion of inhibitory cytokines and direct cell-cell contact.