Hepatitis B virus peptide antigens presented on HLA class I molecules (HBV pMHC class I)

Hepatitis B virus (HBV) peptide antigens presented on HLA class I molecules are critical targets for immunotherapy in patients with chronic hepatitis B and HBV-related hepatocellular carcinoma. These targets consist of viral protein fragments, such as those from the surface (HBsAg), core (HBcAg), or polymerase proteins, which are processed intracellularly and displayed on the cell surface by HLA class I molecules [PMID: 33613465]. Because chronic HBV infection is characterized by a failure of the endogenous T-cell response, therapeutic strategies like TCR-engineered T cells (TCR-T) and bispecific T-cell engagers are designed to bypass this exhaustion by providing high-affinity recognition of these pMHC complexes [PMID: 34153344]. Drugs such as SCG101 and IMC-HBV specifically bind to these epitopes, triggering a potent cytotoxic response against infected hepatocytes or tumor cells containing integrated HBV DNA [PMID: 28469030]. This targeting mechanism is unique because it allows for the potential clearance of the HBV reservoir, including cccDNA and integrated viral sequences, which are not effectively addressed by standard-of-care nucleos(t)ide analogues [PMID: 32103400]. However, the approach carries risks of liver inflammation and cytokine release syndrome as a consequence of the rapid elimination of target cells.

Other names

HBV peptide-MHC complexesHBV-specific HLA-peptide complexesHBV pMHCHepatitis B virus HLA-restricted antigensHBV MHC class I-restricted epitopes

Targeting of viral epitopes presented on the cell surface by engineered T-cell receptors (TCRs) or TCR-like molecules to induce selective lysis of HBV-infected or HBV-integrated tumor cells.