Hepatitis B virus antigen–Human leukocyte antigen class I complex (HBV-HLA-I complex) (HBV-HLA-I complex)

Hepatitis B virus (HBV) antigen–Human leukocyte antigen (HLA) class I complexes are molecular assemblies consisting of HBV-derived peptides (such as those from HBsAg, HBcAg, or HBx proteins) bound within the groove of HLA class I molecules on the cell surface (Tan et al., 2021, Nature Reviews Gastroenterology & Hepatology). In patients with HBV-related hepatocellular carcinoma (HCC), the HBV genome often integrates into the host genome, leading to the constitutive expression and presentation of these viral antigens even in the absence of active viral replication (Tu et al., 2017, Gastroenterology). These complexes serve as highly specific targets for immunotherapy, particularly T-cell receptor (TCR) engineered T-cell therapies, because they are absent from healthy non-infected tissues (Lion TCR, 2024). By engineering T cells to express TCRs that specifically recognize these HBV-pMHC complexes, researchers aim to direct a potent immune response against HCC cells (Qasim et al., 2015, Hepatology). Clinical development of drugs targeting these complexes, such as SCG101 and LioCyx-M, focuses on patients with specific HLA alleles (e.g., HLA-A*02:01) and confirmed HBV-related malignancy (SCG Cell Therapy, 2024; ClinicalTrials.gov NCT05417932). Safety considerations include the risk of "on-target, off-tumor" toxicity if the therapy attacks non-malignant but HBV-infected hepatocytes, potentially leading to severe hepatitis (Tan et al., 2021).

Other names

HBV-pMHC complexHBV peptide-HLA complexHBV-specific pHLAHepatitis B virus antigen-MHC class I complexHBV-specific peptide-MHC complex

Recognition of specific HBV-derived peptides presented by HLA class I molecules by engineered T-cell receptors (TCRs) or TCR-like antibodies, leading to T-cell activation and targeted lysis of HBV-expressing cells.