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Sci Rep. 2018 Mar 2;8(1):3956. doi: 10.1038/s41598-018-22061-x.

Next generation sequencing reveals changes of the γδ T cell receptor repertoires in patients with pulmonary tuberculosis.

Cheng C1, Wang B1,2, Gao L1, Liu J3, Chen X4, Huang H5,6, Zhao Z7,8,9.

Author information

1
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Centre for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
2
Clinical Immunology Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
3
The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450015, China.
4
Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, 518002, China. chenxinchun@szu.edu.cn.
5
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Centre for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. huanghe@ipbcams.ac.cn.
6
Clinical Immunology Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. huanghe@ipbcams.ac.cn.
7
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Centre for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. timjszzd@163.com.
8
Clinical Immunology Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. timjszzd@163.com.
9
CAMS-Oxford University International Center for Translational Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. timjszzd@163.com.

Abstract

Tuberculosis (TB) is a severe global threat to human health. The immune protection initiated by γδ T cells play an important role in mycobacterial infection. Vaccines for Mycobacterium tuberculosis (Mtb) based on γδ T cells provide a novel approach for TB control. In our previous studies, we found a preponderant complementarity-determining region 3 (CDR3) sequence of the γδ T cell receptor (TCR) in TB patients, and successfully identified a tuberculosis antigen that can effectively activate γδ T cells with a reverse genetic strategy. However, due to the throughput limitation of the method we used, the information we obtained about the γδ TCR repertoire and preponderant CDR3 sequences was limited. In this study, we introduced next generation sequencing (NGS) to study the γδ TCR CDR3 repertoires in TB patients. We found that the CDR3δ tended to be more polyclonal and CDR3γ tended to be longer in TB patients; the γδ T cells expressing CDR3 sequences using a Vγ9-JγP rearrangement expanded significantly during Mtb infection. We also identified new preponderant CDR3 sequences during Mtb infection. This study comprehensively characterized the γδ T cell receptor repertoire changes, and provides useful information for the development of new vaccines and adjuvants against TB.

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