Ankrd11 deficiency reverses the dysfunction of chronic HBV-specific T-cell

CD8 ⁺ T cell dysfunction, driven by intricate molecular mechanisms, poses a major obstacle to hepatitis B virus (HBV) clearance in chronic infection. Using a highly humanized mouse model, we identified a T cell receptor (TCR) targeting a dominant epitope essential for HBV clearance in clinical settings. We further uncovered Ankrd11, an epigenetic regulator critical for sustaining CD8 ⁺ T cell dysfunction during chronic infection. Strikingly, Ankrd11 knockout in CD8 ⁺ T cells markedly enhanced HBV-specific T cell proliferation, particularly in immunosuppressive environments, through upregulated AP-1 family gene expression. Additionally, Ankrd11-deficient T cells exhibited robust granzymes production and superior effector functions, resulting in potent antiviral and anti-tumor activity. These findings open new avenues for immunology and virology research, offering promising therapeutic strategies against chronic HBV infection.