Characterization of the TCR β Chain Repertoire in Peripheral Blood from Hepatitis B Vaccine Responders and Non-Responders

Jiezuan Yang,1 Yongtao Li,1 Jing Ye,2 Ju Wang,1 Haifeng Lu,1 Xinsheng Yao3 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Infectious Diseases, Hangzhou, People’s Republic of China; 2Department of Surgical ICU, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 3Department of Immunology, Research Center for Medicine & Biology, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, People’s Republic of ChinaCorrespondence: Jiezuan Yang, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Infectious Diseases, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel +86 571 87236756, Email yangyan@zju.edu.cnBackground: Hepatitis B (HepB) vaccination can effectively prevent the prevalence of hepatitis B virus (HBV) infection. However, the incidence of vaccination failure is about 5∼ 10% and the underlying molecular mechanisms are poorly understood. T cells have an essential role in the recipient’s immune response to vaccine, which could be elucidated by high-throughput sequencing (HTS) and bioinformatics analysis.Methods: We conducted HTS of the T cell receptor β chain (TRB) complementarity-determining region 3 (CDR3) repertoires in eighteen positive responders (responders) and 10 negative responders (non-responders) who all had HepB vaccination, the repertoire features of BV, BJ and V-J genes and their diversity, respectively, were compared between the positive and negative responders using the Mann–Whitney test. Moreover, the relatively conserved motifs in CDR3 were revealed and compared to those in the other group’s report.Results: The diversity of TRB CDR3 and the frequencies of BV27 and BV7-9 are significantly increased for HepB vaccine responders compared to those in non-responders. The motifs of CDR3s in BV27/J1-1, BV27/J2-5, and BV7-9/J2-5, respectively, were most expressed as “NTE”, “QETQ”, and “GG-Q (E)-ETQ”. Moreover, the motif “KLNSPL” was determined in nearly 80% CDR3s in BV27/J1-6 from HepB vaccine responders for the first time.Conclusion: Our results present the comprehensive profiles of TRB CDR3 in the HepB vaccine responders and non-responders after standard vaccination protocol and determine the relatively conservative motifs of CDR3s that may respond to the HepB vaccine. Further results suggest that the profile of TRB repertoire could distinguish the HepB vaccine responders from non-responders and provide a new target for optimizing and improving the efficiency of the HepB vaccine.Keywords: hepatitis B vaccination, hepatitis B surface antibody, complementarity-determining region 3, immune repertoire, high-throughput sequencing