Analysis of the complementarity determining regions β-chain genomic rearrangement using high-throughput sequencing in periphery cytotoxic T lymphocytes of patients with chronic hepatitis B

Huang,Yinuo; Ma,Hong; Wei,Shutang; Luo,Gang; Sun,Ruimin; Fan,Zhibo; Wu,Liping; Yang,Wenyi; Fu,Lin; Wang,Junhui; Han,Dazheng; Lu,Jun

doi:10.3892/mmr.2016.5329

Analysis of the complementarity determining regions β-chain genomic rearrangement using high-throughput sequencing in periphery cytotoxic T lymphocytes of patients with chronic hepatitis B

Authors:
- Yinuo Huang
- Hong Ma
- Shutang Wei
- Gang Luo
- Ruimin Sun
- Zhibo Fan
- Liping Wu
- Wenyi Yang
- Lin Fu
- Junhui Wang
- Dazheng Han
- Jun Lu
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Affiliations: Department of Gastroenterology, First Affiliated Hospital, Henan University, Kaifeng, Henan 475001, P.R. China, Department of Neurology, First Affiliated Hospital, Henan University, Kaifeng, Henan 475001, P.R. China, Department of Physiology, University of Toronto, Toronto, ON M5S1A8, Canada, Cancer Biotherapy Ward, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China
Published online on: May 23, 2016 https://doi.org/10.3892/mmr.2016.5329
Pages: 762-768
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cytotoxic T lymphocytes (CTLs) are important for the recognition of the hepatitis B virus (HBV), mediating immunoprotective mechanisms and determining the clinical outcome following HBV infection. CTLs recognize the invading virus via the T cell receptor (TCR). The aim of the current study was to investigate the variability of TCR in lymphocytes from patients with chronic hepatitis B and whether TCR genomic recombination is regulated by the current treatment strategies. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with chronic hepatitis B and high‑throughput sequencing was performed to analyze the gene expression diversity of β chain complementarity determining region. High‑throughput sequencing produced ~380,000 reads. The sequences of V and J family mRNAs of the β chain V area were analyzed and databases were created for all 30 V family and J family genes. Using the Basic Local Alignment Search Tool, 15 genes were identified to be upregulated in the samples following treatment. Among them, the expression of T cell receptor β variable 28 (TRBV28)_T cell receptor β joining 1‑5 (TRBJ1.5) and TRBV6_TRBJ2.10 were significantly different in the treated samples compared with samples taken prior to treatment. Genomic recombination patterns of TRBV and TRBJ of the β chain V area were observed to be different in the samples following treatment. The data of the current study demonstrated that the genomic rearrangement of the V and J segments of TCR β chain V area may be associated with the chronic progression of HBV and impact on treatment efficacy.

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