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Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection

Cellular & Molecular Immunology volume 11, pages 332–342 (2014)Cite this article

Abstract

The profile of T-cell receptor beta-chain variable (TRBV) genes usually skews in subjects with virus infection or cancer. The gene melting spectral pattern (GMSP) can be used to determine the profile of the TRBV gene family. To explore the portrait of the TRBV family in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection (AHI), peripheral blood mononuclear cells (PBMCs) were separated and further sorted into CD4+ and CD8+ T-cell subsets. The molecular features of the TRBV complementary determining region 3 (CDR3) motifs were determined using GMSP analysis. When a GMSP profile showed a single peak, the monoclonally expanded TRBV gene was cloned and sequenced. Skewed expansions of multiple TRBV genes were observed among the CD4+ and CD8+ T-cell subsets and the PBMCs. The frequency of monoclonally expanded TRBV genes in the CD8+ T-cell subset was significantly higher than that of the CD4+ T-cell subset and the PBMCs. Compared to other members of the TRBV gene family, TRBV11, BV15 and BV20 were predominantly expressed in the repertoire of peripheral blood lymphocytes in recovered AHI subjects. The relatively conserved amino acid motifs of TRBV5.1 and BV20 CDR3 were also detected in the CD4+ and CD8+ T-cell subsets. These results demonstrate the presence of multiple biased TRBV families in recovered AHI subjects. TRBV11, BV15 and BV20, especially from the CD8+ T-cell subset, may be relevant to the pathogenesis of subjects with AHI. The preferentially selected TRBV5.1 and BV20 with the relatively conserved CDR3 motif may be potential targets for personalized treatments of chronic HBV infection.

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Acknowledgements

This work was supported by the Zhejiang Medical Health Fund of China (2012RCA020), the National High-technology R&D Program of China (2013CB531406), the National Science and Technology Major Project (2012ZX10002-006) and the Program for Zhejiang Leading Team of S&T Innovation (2011R09041-02). The authors thank Ms Ping Ye and Ms Haifeng Lu from the Department of Infectious Diseases at the First Affiliated Hospital, College of Medicine, Zhejiang University for their help in collecting samples for this study.

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  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

    Jiezuan Yang, Jiajia Chen, Jianqin He, Yirui Xie, Yixing Zhu, Hongcui Cao & Lanjuan Li

  2. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China

    Jiezuan Yang, Jiajia Chen, Jianqin He, Yirui Xie, Yixing Zhu, Hongcui Cao & Lanjuan Li

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Correspondence to Lanjuan Li.

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Yang, J., Chen, J., He, J. et al. Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection. Cell Mol Immunol 11, 332–342 (2014). https://doi.org/10.1038/cmi.2014.22

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