Hepatitis B virus peptide-HLA class I complex (HBV pHLA-I)

The Hepatitis B virus (HBV) peptide-HLA class I complex is a molecular target consisting of viral protein fragments (epitopes) bound to and presented by Human Leukocyte Antigen (HLA) class I molecules on the surface of infected hepatocytes and HBV-related hepatocellular carcinoma (HCC) cells [4, 14, 16]. These complexes are the primary signals recognized by the host's CD8+ cytotoxic T lymphocytes (CTLs) to identify and eliminate virally infected cells [12, 16]. In chronic HBV infection, the immune system often fails to clear the virus due to T-cell exhaustion and impaired antigen presentation, allowing the virus to persist and potentially lead to cirrhosis or HCC [10, 12]. Therapeutic strategies targeting these complexes include T-cell receptor-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (e.g., ImmTAVs), which redirect functional T cells to recognize and lyse cells displaying specific HBV peptides, such as those derived from the surface (HBsAg), core (HBcAg), or polymerase proteins [1, 11, 18]. A significant challenge in targeting this complex is "on-target, off-tumor" toxicity, where the therapy may cause extensive lysis of non-malignant but infected hepatocytes, potentially leading to severe liver inflammation or fulminant hepatitis [1, 2, 3].

Other names

Hepatitis B virus peptide antigens presented on HLA class I on infected hepatocytesHBV peptide-MHC class I complexHBV peptide-HLA complexHBV-specific T-cell epitopesHBV pHLA

Redirection of T-cell cytotoxicity toward HBV-infected or malignant hepatocytes via engineered T-cell receptors or bispecific molecules.