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The Hepatitis B surface antigen-derived peptide–HLA-A*02:01 complex (HBsAg–HLA-A*02:01) is a peptide-major histocompatibility complex (pMHC) class I molecule presented on the surface of cells infected with the Hepatitis B virus (HBV) or HBV-related hepatocellular carcinoma (HCC) cells (PMID: 34556545). This complex consists of an 8-10 amino acid epitope from the HBsAg protein, such as the highly conserved 183-191 or 335-343 sequences, bound to the HLA-A*02:01 allele (PMID: 28834721). It serves as a specific molecular target for CD8+ cytotoxic T lymphocytes (CTLs), which recognize the complex via their T-cell receptors (TCRs) to initiate an immune response (PMID: 30249040). In chronic HBV infection, the natural T-cell response against this complex is typically exhausted or absent, allowing for viral persistence and potential oncogenesis (PMID: 31160388). Therapeutic strategies targeting this complex include TCR-redirected T-cell therapies (TCR-T), such as SCG101, and therapeutic vaccines like HepTcell, which aim to restore or provide a robust immune attack against HBV-positive cells (SCG Cell Therapy, 2023; Altimmune, 2023). By specifically targeting the HBsAg–HLA-A*02:01 complex, these treatments can selectively eliminate infected hepatocytes and tumor cells while minimizing damage to healthy, non-infected tissue.
T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and lysis of target cells (PMID: 30249040).
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