Hepatitis B surface antigen-derived peptide–major histocompatibility complex (HBsAg-pMHC)

Hepatitis B surface antigen (HBsAg)-derived peptide–major histocompatibility complex (MHC) molecules are critical immunological targets for the treatment of chronic Hepatitis B virus (HBV) infection and HBV-related hepatocellular carcinoma (HCC) (scgcell.com, 2024). These complexes are formed when intracellularly processed HBsAg fragments, such as the S20-28 epitope (FLLTRILTI), are loaded onto MHC Class I molecules (typically HLA-A*02:01) and transported to the cell surface for presentation to the immune system (nih.gov, 2023). T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes specifically recognize these pMHC complexes, initiating a signaling cascade that leads to the destruction of the presenting cell (asm.org, 2025). In the context of chronic HBV, the natural T-cell response is often exhausted or insufficient, leading to viral persistence and potential oncogenesis (nih.gov, 2025). Therapeutic interventions, such as TCR-engineered T-cell (TCR-T) therapies like SCG101 and LioCyx-M004, are designed to bypass this exhaustion by providing high-affinity TCRs that specifically bind these HBsAg-pMHC complexes (liontcr.com, 2021). This approach aims to selectively eliminate HBV-infected hepatocytes and HCC cells while sparing healthy tissue, though challenges such as HLA restriction and cytokine release syndrome remain significant considerations (biospace.com, 2025).

Other names

HBsAg-peptide–HLA complexHBV surface antigen peptide-MHCHBsAg-pMHC complexHepatitis B surface antigen-derived peptide–human leukocyte antigen complexEnv183-191/HLA-A*02:01 complexS20-28/HLA-A*02:01 complex

T-cell receptor-mediated recognition of the peptide-MHC complex on the surface of infected or malignant cells leads to the activation of cytotoxic T lymphocytes, resulting in the targeted lysis of HBV-infected or HBV-integrated malignant cells through the release of perforin, granzymes, and antiviral cytokines.