Hepatitis B virus core antigen-derived peptides presented on Major Histocompatibility Complex molecules (HBcAg-pMHC)

Hepatitis B virus core antigen (HBcAg)-derived peptides presented on Major Histocompatibility Complex (MHC) molecules are critical targets for immunotherapies aimed at treating chronic hepatitis B (CHB) and HBV-related hepatocellular carcinoma (HCC). During infection, the HBV core protein is intracellularly processed into short peptides, such as the highly immunodominant HBcAg 18-27 epitope, which are then displayed on the cell surface by HLA molecules, most commonly HLA-A*02:01 (PMID: 15507521, 21454477). These peptide-MHC (pMHC) complexes serve as the primary signal for CD8+ T-cell recognition; however, in chronic infection, endogenous T-cell responses are typically exhausted or absent. Modern therapeutic strategies, including TCR-engineered T-cell (TCR-T) therapies like SCG101, utilize high-affinity receptors to specifically target these complexes, bypassing natural immune tolerance to induce the death of infected hepatocytes or tumor cells (NCT05417932). This approach aims to achieve a functional cure for HBV by reducing viral reservoirs and clearing cells with integrated HBV DNA.

Other names

HBV core peptide-MHC complexHBcAg peptide-HLA complexHBV core 18-27 peptide-HLA-A*02:01Hepatitis B virus core antigen epitopesHBcAg-derived pMHC

Therapeutic agents such as TCR-engineered T cells (TCR-T) or TCR-like antibodies specifically bind to the HBV core peptide-MHC complex on the surface of infected or malignant cells, triggering T-cell mediated cytotoxicity and the release of antiviral cytokines to eliminate the target cells.