Hepatitis B surface antigen peptide S20–28 presented by Human Leukocyte Antigen A*02:01 (HBsAg S20–28/HLA-A*02:01)

The HBsAg S20–28 peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) found on the surface of cells infected with the Hepatitis B virus (HBV) or hepatocellular carcinoma (HCC) cells containing integrated HBV DNA (PMID: 35713357). The peptide sequence, FLLTRILTI, is derived from the small surface protein (S) of HBV and is processed and loaded onto the HLA-A*02:01 molecule for presentation to CD8+ cytotoxic T lymphocytes (PMID: 12433357). This complex serves as a critical epitope for the cellular immune response; however, in chronic HBV infection, endogenous T-cell responses against this epitope are often exhausted or deleted (PMID: 25860614). Consequently, this pMHC has become a primary target for adoptive cell therapies, particularly T-cell receptor-engineered T-cell (TCR-T) therapies like SCG101, which are designed to bypass natural immune tolerance (SCG Cell Therapy, 2023). By targeting this specific complex, these therapies can selectively eliminate HBV-infected hepatocytes and HBV-positive tumor cells while sparing healthy tissue that does not express the viral antigen. This approach is currently being investigated as a potential functional cure for chronic hepatitis B and a treatment for HBV-related liver cancer (NCT05417932).

Other names

HBV S20-28/HLA-A*02:01FLLTRILTI-HLA-A*02:01 complexHBsAg 20-28 peptide-MHC complexHepatitis B virus surface antigen S20-28 epitope

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to targeted lysis of HBV-infected or HBV-integrated cells.