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

The Hepatitis B virus (HBV) peptide–Human leukocyte antigen (HLA) class I complex is a molecular assembly consisting of a viral peptide fragment bound within the groove of an HLA class I molecule on the surface of infected hepatocytes or HBV-related hepatocellular carcinoma (HCC) cells [1]. This complex serves as the primary signal for recognition by CD8+ cytotoxic T lymphocytes (CTLs) via their T-cell receptors (TCRs) [1, 5]. In the context of chronic HBV infection and HBV-HCC, the presentation of these viral antigens is often insufficient to trigger a robust immune response due to T-cell exhaustion or immune evasion [1]. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies, such as SCG101 and LioCyx-M, and bispecific T-cell engagers like IMC-HBV, which aim to redirect the immune system to specifically eliminate cells harboring the viral genome or integrated HBV DNA [2, 3, 4]. By focusing on intracellularly derived viral peptides presented on the cell surface, these therapies can target cells that do not necessarily express high levels of surface viral proteins [1]. However, challenges include the high polymorphism of HLA alleles and the risk of severe liver inflammation (hepatitis) resulting from the mass destruction of infected hepatocytes [1, 2].

Other names

HBV pMHC complexHBV-specific peptide-MHC complexHBV-HLA complexHepatitis B virus antigen-HLA class I complexHBV-HLA-A*02:01 complex

The mechanism of action involves the specific recognition of HBV-derived peptides (such as those from HBsAg, HBcAg, or HBV polymerase) presented by HLA class I molecules on the cell surface by engineered T-cell receptors (TCRs) or TCR-like antibodies, leading to the activation of cytotoxic T-cell responses and the subsequent lysis of the target HBV-infected or malignant cell [1, 2].