In chronic Hepatitis B Virus (HBV) infection, viral load is higher in male patients compared to females, increasing their risk for severe complications such as liver cirrhosis and hepatocellular carcinoma. However, the underlying mechanisms remain elusive. Data from animal models and own preliminary data suggest a differential viral control by HBV-specific CD8+ T cells in females and males. It is therefore the goal of this research proposal to define the immunological mechanisms responsible for the gender-specific differences. Specifically, I will analyze the overall immune landscape and repertoire, differentiation and function of HBV-specific CD8+ T cells in male versus female patients with chronic HBV infection using flow cytometry, single cell RNA sequencing and cytometry time of flight.