Hepatitis B surface antigen-derived peptide–Human leukocyte antigen-A*02:01 complex (HBsAg-peptide–HLA-A*02:01) (HBsAg-peptide–HLA-A*02:01)

The Hepatitis B surface antigen-derived peptide–Human leukocyte antigen-A*02:01 complex (HBsAg-peptide–HLA-A*02:01) is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of cells infected with the Hepatitis B virus (HBV) or HBV-integrated hepatocellular carcinoma (HCC) cells [1]. This complex consists of an immunodominant 9-amino acid fragment, typically HBsAg 183-191 (FLLTRILTI), derived from the viral surface protein and bound to the HLA-A*02:01 molecule [2]. In patients with chronic HBV or HBV-related HCC, this pMHC serves as a highly specific target for cellular immunotherapies, distinguishing infected or malignant cells from healthy, non-infected tissue [3]. Therapeutic agents such as SCG101 and LioCyx-M utilize engineered T-cell receptors (TCR-T) to recognize this complex and initiate a cytotoxic immune response against the target cells [4][5]. Additionally, TCR-like antibodies and CAR-T cells, such as ET1402L1, have been developed to target this specific epitope with high affinity [6]. By targeting this specific pMHC, these therapies aim to achieve a functional cure for HBV or provide a targeted treatment for HBV-associated liver cancer while minimizing damage to non-infected tissues [7]. However, the widespread expression of HBsAg in the livers of chronic carriers poses a significant challenge regarding potential on-target hepatotoxicity and the management of the inflammatory response [8]. Clinical monitoring of liver enzymes and cytokine levels is essential during treatment to ensure patient safety [9].

Other names

HBsAg183-191/HLA-A*02:01HBV-specific pMHC complexHBsAg-HLA-A2 complexHepatitis B surface antigen peptide-MHC

Recognition by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce cytotoxic T-lymphocyte (CTL) mediated killing of cells presenting the viral epitope.