Hepatitis B virus peptide–HLA-A*02:01 complex (HBV-HLA-A*02:01)

The Hepatitis B virus (HBV) peptide–HLA-A*02:01 complex is a molecular assembly presented on the surface of hepatocytes during chronic HBV infection and in HBV-related hepatocellular carcinoma (HCC) (Boni et al., 1998). It comprises a specific viral epitope, such as the highly conserved core protein fragment HBcAg 18-27, bound to the Class I Major Histocompatibility Complex (MHC) molecule HLA-A*02:01 (Gehring et al., 2011). This complex acts as a ligand for T-cell receptors (TCRs), signaling the presence of intracellular viral infection or the expression of integrated viral DNA in tumor cells. In the context of chronic infection, the endogenous T-cell response against this target is typically exhausted, leading to viral persistence and oncogenesis. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers, which aim to redirect the immune system to lyse target cells (SCG Cell Therapy, 2023). Clinical candidates like SCG101 and IMC-HBV are designed to recognize these specific pMHC complexes with high sensitivity and specificity (Immunocore, 2022). Because the target is specific to cells presenting HBV antigens, it offers a pathway for precision immunotherapy in HCC patients who are HLA-A*02:01 positive. However, the destruction of a large number of infected hepatocytes can lead to significant liver inflammation and transient ALT flares, requiring careful clinical management.

Other names

HBV pMHC complexHBV-specific peptide-MHCHBV-derived epitope-HLA-A*02:01 complexHBV core 18-27 HLA-A*02:01HBcAg 18-27 HLA-A*02:01

Redirection of T-cell cytotoxicity via high-affinity binding of engineered T-cell receptors (TCRs) or TCR-like antibodies to viral peptides presented by HLA-A*02:01 on the cell surface.