Assessing the chronic hepatitis B adaptive immune response by profiling specific T-cell receptor repertoire

Challenges in assessing hepatitis B virus (HBV)-specific T cell immunity as an immunological biomarker still remain in chronic hepatitis B (CHB), such as the requirement of large quantities of cells. This study aims to conveniently assess HBV-specific T cells immunity in chronic HBV infected patients. We obtained T cell receptor beta chains (TCR beta s) from public databases and six acute hepatitis B patients to establish an HBV-specific TCR beta s dataset. For some TCRs from one acute patient, their specificities and epitopes were verified. The potential HBVspecific TCR beta s from CHB patients were analyzed using GLIPH2 and established dataset. By analyzing two antiviral therapy cohorts including 42 CHB patients, we showed that individuals with better therapy response may depend more on newly emerging potential HBV-specific TCR beta s. In a cross-sectional study containing 207 chronic HBV infected patients, the results exhibited that the characteristics of potential HBV-specific clusters were divergent between CHB and hepatocellular carcinoma patients. Our strategy could profile potential HBVspecific TCR beta repertoire using a small blood sample, which will complement traditional methods for assessing the HBV-specific T cell immunity.