Comprehensive evaluation of the αβ-TCR repertoire profile in hepatitis B vaccine-positive responders and patients with chronic hepatitis B

Abstract

T cells play a vital role in hepatitis B virus (HBV) infection, mediating both protective immunity and immunopathology. Deep profiling of the T cell receptor (TCR) complementarity-determining region 3 (CDR3) provides critical insights into T cell composition and function. However, the characteristics of the TCR α-chain (TRA) and β-chain (TRB) repertoires in individuals with different HBV infection and vaccination statuses remain incompletely understood. We employed high-throughput sequencing (HTS) to profile the TRA and TRB CDR3 repertoires in peripheral blood mononuclear cells (PBMCs) from 6 inoculation-positive responders (IPR) to hepatitis B (HepB) vaccination, 6 individuals with chronic hepatitis B (CHB), and 5 healthy donors (HD). We systematically compared the frequency, diversity, similarity, and V/J segment usage of TRA and TRB CDR3s across the three groups. The CHB group exhibited significantly fewer unique TRA and TRB CDR3s than both IPR and HD groups. Overlap analysis revealed that the BUB index for TRAV was significantly higher in IPR than in CHB and HD groups ( P = 0.0073 and P = 0.0317, respectively), while for TRBV, a significantly higher BUB index was observed only between IPR and CHB groups ( P = 0.0002). Additionally, identical TRA CDR3s were preferentially shared among individuals within each group, whereas TRBJ usage remained relatively stable across groups. Collectively, our findings delineate distinct CDR3 repertoire characteristics of circulating T cells in IPR and CHB, which may enhance understanding of the protective response to HepB vaccination and inform future investigations into TRA- and TRB-based strategies for HBV diagnosis and prevention.