Restricted TcR β chain CDR3 Clonotype Is Associated with Resolved Acute Hepatitis B (AHB) patients with HBsAb

Abstract

Background: T cells play an important role in the prognosis of HBV infection, and are involved in the seroconversion of a patient from HBsAb negative to HBsAb positive. To compare the T-cell receptor beta chain variable region (TcRBV) complementarity-determining region 3 (CDR3) in subjects with or without HBsAg seroconversion to HBsAb, the TcRBV was determined using high throughput sequencing (HTS). Methods: Clonotype and diversity of CDR3 in peripheral blood mononuclear cells (PBMCs) of subjects with resolved acute hepatitis B (AHB, HBsAb+, and HBsAg-) (n = 5), chronic hepatitis B (CHB, HBsAb-, and HBsAg+) (n = 5), and healthy controls (HC, HBsAb-, and HBsAg-) (n = 3) were determined and analyzed using HTS (MiSeq). Findings: The overlapping rate of CDR3 clones for any two samples in the AHB, CHB, and HC groups were 2.00% (1.74–2.30%), 1.77% (1.43–2.61%), and 1.82% (1.62%–2.12%), respectively; no significant difference was found among the three groups by Kruskal-Wallis H test. In addition, among the top 10 cumulative frequencies of clonotypes, only the frequency of clonotype (TcRBV20-1/TcRBD1/TcRBJ1-2) in the AHB group was lower than that in the HC group (P 0.05). Interpretation: Thus, there are 57 TcRBV clonotypes that may be related to HBsAg seroconversion in AHB subjects, but the diversity of TcRBV CDR3 is not significantly related to the HBsAb positive status. Funding Statement: This work was supported by National Natural Science Foundation of China (81671557), the Zhejiang Provincial Natural Science Foundation of China (LY19H190004), and the National Science and Technology Major Project (2018ZX10101-001). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: This project and protocols involving human subjects were approved by the ethics committee of the First Affiliated Hospital of Zhejiang University. Informed consent was obtained from each subject included in the study.