Hepatitis B surface antigen peptide-MHC class I complex (HBsAg pMHC)

The Hepatitis B surface antigen (HBsAg) peptide-MHC class I complex is a therapeutic target consisting of a specific viral epitope, most commonly the immunodominant HBsAg 183-191 (FLLTRILTI) peptide, bound to a Major Histocompatibility Complex (MHC) class I molecule, typically HLA-A*02:01 [5, 13]. This complex is naturally presented on the surface of hepatocytes infected with the Hepatitis B virus (HBV) and on hepatocellular carcinoma (HCC) cells where HBV DNA has integrated into the host genome [6, 13]. In chronic HBV infection and HBV-related HCC, these complexes serve as specific markers that allow the immune system to distinguish diseased cells from healthy ones [15, 16]. Therapeutic strategies targeting this complex include T-cell receptor-engineered T-cell (TCR-T) therapies, such as SCG101 and LioCyx-M, which utilize high-affinity TCRs to recognize and eliminate target cells [10, 16, 18]. Upon binding, these therapies trigger direct cytotoxic cell lysis and the release of pro-inflammatory cytokines like interferon-gamma [13, 18]. While highly specific, targeting this complex carries risks such as cytokine release syndrome and transient hepatotoxicity due to the destruction of infected hepatocytes [11, 18]. Clinical trials have demonstrated that targeting this pMHC complex can lead to significant reductions in serum HBsAg levels and tumor shrinkage in patients with advanced HCC [10, 11, 18].

Other names

HBsAg 183-191/HLA-A*02:01 complexHBsAg-derived peptide-MHC class IEnv183-191/HLA-A*02:01HBsAg peptide-HLA complexHBsAg pMHC complex

T-cell receptor (TCR) mediated recognition and lysis of cells presenting the viral peptide-MHC complex