Hepatitis B virus surface antigen-derived peptide-MHC complex (HBsAg-pMHC)

Hepatitis B virus surface antigen (HBsAg)-derived peptides presented on major histocompatibility complex (MHC) molecules are the primary targets for T-cell recognition of HBV-infected cells (asm.org, nih.gov). These complexes consist of short viral peptide fragments bound within the groove of MHC class I molecules, such as HLA-A*02:01, and are expressed on the surface of hepatocytes during active infection or on hepatocellular carcinoma (HCC) cells with integrated HBV DNA (nih.gov, bmj.com). In chronic infection, the endogenous T-cell response against these complexes is often exhausted or deleted, allowing the virus to persist (tandfonline.com). Modern immunotherapies, including T-cell receptor-engineered T-cell (TCR-T) therapy and bispecific T-cell engagers (TCEs), are designed to bypass this exhaustion by redirecting functional T cells to recognize and eliminate cells presenting these specific viral epitopes (scgcell.com, onclive.com). Upon binding, these therapies trigger T-cell activation, leading to the release of cytotoxic granules and cytokines like interferon-gamma, which results in the targeted destruction of infected or malignant cells (clinicaltrialsarena.com, bmj.com). Clinical candidates like SCG101 have demonstrated the ability to significantly reduce serum HBsAg and tumor burden in patients (cgtlive.com, scgcell.com). However, these therapies are restricted to patients carrying the specific HLA allele recognized by the engineered receptor (nih.gov). Safety monitoring is critical due to the risk of cytokine release syndrome and transient hepatotoxicity associated with the rapid clearance of target cells (aacrjournals.org, nih.gov).

Other names

HBsAg peptide-MHC complexHBsAg-HLA-A*02:01 complexHBV surface antigen epitope-MHC complexHBsAg-pMHCHBV Env-derived peptide-HLA complex

T-cell redirection and activation via engineered T-cell receptors (TCRs) or bispecific molecules that bind specifically to the HBsAg peptide-MHC complex, leading to the cytolytic and non-cytolytic elimination of HBV-infected or HBV-integrated cells (scgcell.com, bmj.com).