Hepatitis B virus surface antigen peptide-HLA class I complex (HBsAg-HLA-I complex)

The Hepatitis B virus surface antigen (HBsAg) peptide-HLA class I complex is a molecular assembly consisting of an 8-10 amino acid fragment derived from the HBV surface protein bound within the groove of a Class I Human Leukocyte Antigen (HLA) molecule, most commonly HLA-A*02:01 [PMID: 34153341]. This complex is expressed on the surface of hepatocytes during active HBV infection or in hepatocellular carcinoma (HCC) cells where HBV DNA has integrated into the host genome [PMID: 33865022]. It serves as the primary ligand for the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, which are responsible for the targeted destruction of infected or malignant cells [PMID: 32553506]. In the context of chronic hepatitis B, the natural T-cell response is often dysfunctional or exhausted, leading to viral persistence; therefore, this complex is a major target for adoptive cell therapies like TCR-engineered T cells (TCR-T) [Source: SCG Cell Therapy]. Drugs targeting this complex, such as SCG101, utilize high-affinity TCRs to recognize the pMHC and trigger a potent antiviral and anti-tumor response, aiming for functional cure or tumor regression [Source: ClinicalTrials.gov NCT05271630]. Therapeutic challenges include the high polymorphism of HLA molecules, requiring patient-specific HLA matching, and the risk of off-target toxicity if the TCR cross-reacts with similar self-peptides [PMID: 33865022].

Other names

HBsAg peptide-MHC complexHBV surface antigen-HLA complexpMHC complex (HBsAg)HBsAg-HLA-A*02:01 complexHepatitis B surface antigen-derived peptide-HLA-A2 complex

Engineered T-cell receptors (TCRs) or TCR-like antibodies specifically bind to the HBsAg peptide presented by HLA class I molecules, triggering cytotoxic T-lymphocyte activation, secretion of antiviral cytokines (e.g., IFN-gamma), and direct lysis of HBV-infected or malignant cells [PMID: 34153341, PMID: 33865022].