T-cell receptor recognizing Hepatitis B surface antigen-derived peptide–MHC class II complexes (HBsAg-specific MHC-II-restricted TCR)

The T-cell receptor (TCR) recognizing HBsAg-derived peptide–MHC class II complexes is a specialized immune receptor engineered to target Hepatitis B virus (HBV) surface antigens presented by Major Histocompatibility Complex (MHC) class II molecules. While most TCR-based therapies for HBV focus on MHC class I to engage CD8+ cytotoxic T cells, MHC class II-restricted TCRs are designed to harness CD4+ T cells, which are essential for orchestrating a durable and effective immune response (Bertoletti & Tan, 2020). These receptors typically recognize specific epitopes, such as HBsAg 161–180, presented by alleles like HLA-DPB1*04:01, which is highly prevalent in certain populations (Koh et al., 2018). Upon binding, the TCR triggers CD4+ T cell activation, leading to the secretion of antiviral cytokines like interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), as well as providing help to B cells and CD8+ T cells (Wisskirchen et al., 2019). This target is primarily utilized in the development of adoptive T-cell therapies (TCR-T) for patients with chronic hepatitis B (CHB) and HBV-related hepatocellular carcinoma (HCC). The therapeutic goal is to overcome the T-cell exhaustion characteristic of chronic infection and achieve a functional cure or tumor regression (Tan et al., 2015).

Other names

HBsAg-specific MHC class II-restricted T-cell receptorMHC-II restricted HBV TCRCD4+ HBV-specific T-cell receptorHBsAg-specific TCR

Recognition of HBsAg-derived peptides presented by MHC class II molecules on the surface of HBV-infected cells or antigen-presenting cells, leading to the activation of CD4+ T cells and the subsequent release of antiviral cytokines (e.g., IFN-gamma, TNF-alpha) and coordination of the broader immune response.