Hepatitis B virus peptide-MHC complex (HBV pMHC)

The Hepatitis B virus (HBV) peptide-MHC complex is a therapeutic target consisting of viral antigenic fragments, such as those derived from the surface antigen (HBsAg) or core antigen (HBcAg), presented by Major Histocompatibility Complex (MHC) molecules on the surface of infected hepatocytes and HBV-related hepatocellular carcinoma (HCC) cells. These complexes serve as the specific recognition sites for T-cell receptors (TCRs), which are often engineered into autologous T cells (TCR-T therapy) or targeted by TCR-mimic antibodies to overcome the immune exhaustion typical of chronic HBV infection. By binding to these pMHC complexes, therapeutic agents trigger potent T-cell activation, leading to the cytolytic destruction of diseased cells and the non-cytolytic suppression of viral replication through cytokine release (e.g., IFN-gamma). Clinical candidates like SCG101 and LioCyx-M target specific epitopes such as HBsAg S20-28 in the context of HLA-A*02:01, demonstrating the potential for significant viral load reduction and tumor regression. However, the therapy carries risks of on-target off-tumor toxicity, as it may also eliminate healthy HBV-infected hepatocytes, potentially leading to transient liver inflammation or failure.

Other names

Hepatitis B virus peptide-MHC complexHBV pMHC complexHBsAg peptide-HLA complexHBcAg peptide-HLA complexHBV-specific TCR targetHepatitis B virus peptide-major histocompatibility complex

Engineered T-cell receptors (TCRs) or TCR-mimic antibodies bind to specific HBV peptides presented by MHC molecules on the surface of infected or malignant hepatocytes, triggering T-cell mediated cytolysis and cytokine-driven viral suppression.