Hepatitis B virus surface antigen peptide–Major Histocompatibility Complex (HBsAg-pMHC)

The Hepatitis B virus surface antigen peptide–Major Histocompatibility Complex (HBsAg-pMHC) is a molecular assembly consisting of processed peptides derived from the HBV surface protein presented on the surface of infected hepatocytes or tumor cells by MHC (HLA) molecules (PubMed: 33806153). This complex serves as a critical recognition signal for the host's immune system, specifically for CD8+ cytotoxic T lymphocytes (CTLs). In the context of chronic HBV infection and HBV-related hepatocellular carcinoma (HCC), the endogenous T-cell response is often exhausted or insufficient to clear the virus or malignant cells (PubMed: 31534173). Consequently, the HBsAg-pMHC complex has emerged as a high-priority therapeutic target for adoptive cell therapies, such as TCR-engineered T cells (TCR-T), and TCR-like bispecific antibodies (PubMed: 37435030). These therapies, such as SCG101 and LioCyx-M, are designed to bypass natural immune tolerance by providing high-affinity receptors that specifically bind the HBsAg-pMHC complex, triggering targeted lysis of HBV-infected or cancerous cells while sparing healthy tissue that does not express the viral antigen (ClinicalTrials.gov: NCT05417932). This approach is particularly relevant for HCC where HBV DNA is integrated into the host genome, leading to persistent HBsAg expression even in the absence of active viral replication (PubMed: 34155116). Clinical trials are currently evaluating the safety and efficacy of these agents, focusing on potential side effects like cytokine release syndrome and liver inflammation (PubMed: 36210345).

Other names

HBsAg-HLA complexHBV surface antigen-HLA complexHBsAg peptide-MHCHBV-specific pMHC

T-cell receptor (TCR) mediated recognition and subsequent T-cell directed lysis of target cells.