Hepatitis B virus peptide–Human leukocyte antigen complex (HBV-HLA complex) (HBV-HLA complex)

Hepatitis B virus (HBV) peptide–Human leukocyte antigen (HLA) complexes are molecular assemblies found on the surface of HBV-infected hepatocytes and HBV-related hepatocellular carcinoma (HCC) cells. These complexes consist of short viral peptide fragments, derived from HBV proteins such as the core (HBcAg), surface (HBsAg), or polymerase (HBp), which are processed and presented by HLA class I molecules, most commonly HLA-A*02:01 (Tan et al., 2019, Gastroenterology). Their primary biological function is to signal the presence of intracellular viral infection to the host's immune system, specifically to CD8+ cytotoxic T lymphocytes (CTLs) (Bertoletti & Ferrari, 2016, Journal of Hepatology). In chronic HBV infection and associated malignancies, the endogenous T-cell response is often dysfunctional or exhausted, allowing the virus and tumor cells to persist (Maini & Pallett, 2018, Clinical & Experimental Immunology). Consequently, these complexes have become high-priority therapeutic targets for immunotherapies, including T-cell receptor-engineered T-cell (TCR-T) therapies and TCR-like bispecific molecules (Qiao et al., 2022, Journal of Hepatology). These treatments are designed to bypass immune exhaustion by providing high-affinity recognition of the HBV-HLA complex, leading to the selective destruction of infected or cancerous cells while minimizing damage to non-infected tissues (Meng et al., 2021, Frontiers in Oncology).

Other names

HBV pMHCHBV-specific peptide-MHC complexHBV-HLA-A*02:01 complexHBV-derived peptide-HLA complexHBV-Ag/HLA complex

Targeting of the HBV peptide–HLA complex by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce T-cell mediated cytotoxicity and cytokine production against infected or malignant cells.