[Analysis of T cell receptor BV dominant usage and CDR3 sequences during acute exacerbation in patients with chronic hepatitis B]
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Published on: February 28, 2019
Guang-wen Zhang1, Xin-sheng Yao, Shi-wu Ma
1Department of Infectious Diseases, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.
Insights
Cellular immunology, specifically T cell receptor (TCR) analysis, reveals clonal expansion in chronic hepatitis B (CHB) patients during acute exacerbations, indicating its role in liver inflammation.
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Context:
- Chronic hepatitis B (CHB) is a significant global health concern.
- The precise mechanisms of CHB pathogenesis, particularly the role of cellular immunity, require further elucidation.
- Understanding T cell responses in CHB is crucial for developing targeted therapies.
Purpose:
- To investigate the involvement of cellular immunology in CHB pathogenesis.
- To analyze T cell receptor (TCR) beta chain variable region (BV) gene family usage and beta chain complementarity determining region 3 (CDR3) sequences in CHB patients.
- To assess T cell clonal expansion and repertoire diversity in CHB during acute exacerbations.
Summary:
- Peripheral blood mononuclear cells from 8 CHB patients during acute exacerbations and 4 healthy controls were analyzed using immunoscope technology and CDR3 sequencing.
- TCR BV repertoire in healthy donors exhibited a Gaussian distribution.
- CHB patients displayed distinct TCR BV family usage and CDR3 sequences, indicative of clonal T cell expansion, potentially stimulated by hepatitis B virus (HBV) epitopes.
Impact:
- This study highlights the significant clonal expansion of peripheral blood T cells in CHB patients during acute exacerbations.
- The findings underscore the critical role of cellular immunology in the inflammatory processes underlying CHB liver disease.
- Results provide insights into T cell-mediated immune responses in CHB, paving the way for novel immunotherapeutic strategies.
Objectives:
To understand the role cellular immunology plays in the pathogenesis of chronic hepatitis B (CHB) through analysis of T cell receptor (TCR) beta chain variable region gene (BV) family dominant usage and beta chain complementarity determining region3 (CDR3) sequences of peripheral blood mononuclear cells of the patients.
Methods:
TCR BV families were amplified by inverse polymerase chain reaction (RT-PCR), and the dominant usage of BV families and CDR3 repertoire were analyzed by immunoscope technology for 8 CHB patients during their acute exacerbations and for 4 healthy blood donors who served as controls. The clonality of the T cells suspected by immunoscope was further confirmed by CDR3 sequencing.
Results:
The TCR BV CDR3 repertoire of the 4 healthy blood donors showed a Gaussian distribution. In the 8 CHB patients, however, the clonal expansion of T cells showed different TCR BV families with each patient. The T cells of the clonal expansion shared different CDR3 sequences.
Conclusion:
The peripheral blood T cells of CHB patients during their acute exacerbation showed significantly a clonal expansion and their T cell clonal expansion may be stimulated by several HBV epitopes. These results indicate that cellular immunology is involved in the pathogenesis of the liver inflammation process of CHB.
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