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

The Hepatitis B surface antigen peptide-Major Histocompatibility Complex (HBsAg-pMHC) is a molecular target consisting of specific peptide fragments derived from the HBV surface protein presented on the surface of infected hepatocytes or HBV-integrated hepatocellular carcinoma (HCC) cells by Human Leukocyte Antigen (HLA) molecules (Tan et al., 2019, Gastroenterology). This complex serves as the primary ligand for the T-cell receptor (TCR) of HBV-specific CD8+ T cells, which are typically exhausted or absent in patients with chronic hepatitis B (Bertoletti & Ferrari, 2016, Gut). Therapeutic interventions such as TCR-engineered T-cell (TCR-T) therapies (e.g., SCG101, LioCyx-M) and TCR-like bispecific molecules are designed to specifically recognize HBsAg-pMHC to induce the lysis of infected or malignant cells (Koh et al., 2023, Journal of Hepatology). By targeting these complexes, these therapies aim to achieve a functional cure for HBV or treat HBV-related HCC by eliminating the reservoir of cells expressing viral antigens. The specificity of this target is determined by both the viral peptide sequence and the host's HLA genotype, most commonly HLA-A*02:01 in clinical development (Wisskirchen et al., 2019, Journal of Clinical Investigation).

Other names

HBsAg-HLA complexHBV surface antigen peptide-MHCHBsAg-MHC class I complexHBsAg-pHLA complex

Recognition by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce cytotoxic killing of HBV-infected or HBV-integrated cells via the release of perforins, granzymes, and pro-inflammatory cytokines.