Yang Guiqi, Ou Minglin, Chen Huaizhou, Guo Changchun, Chen Jiejing, Lin Hua, Tang Donge, Xue Wen, Li Wenlong, Sui Weiguo, Dai Yong
Guangxi Key Laboratory of Metabolic Diseases Research, Guilin 541002, P.R. China.
Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China.
Oncotarget. 2018 Oct 2;9(77):34506-34519. doi: 10.18632/oncotarget.26138.
Liver cirrhosis of hepatitis B is an immune-related disease in which liver cells die during the body's immune system activation to clear the virus, and the progress is closely related to T lymphocytes. T lymphocyte cells recognise antigens, specifically by major histocompatibility complex (MHC), through a membrane protein T cell receptor (TCR). Here, we used high throughput immune repertoire sequencing technique to study the characteristics and diversity of the TCR repertoire between patients who underwent liver transplantation and healthy controls (NC). We sequenced the TCR β-chain complementary-determining region 3 (CDR3) repertoire in peripheral blood mononuclear cells (PBMCs) from 6 liver transplantation patients before transplantation (Pre) and on the first (Post1) and seventh days (Post7) after transplantation along with 6 NC. We observed that the distributions of CDR3, VD indel, and DJ indel lengths were similar among the Pre, Post1, Post7 and NC groups. We found that the TCR repertoire diversity of transplantation groups was relatively lower compared to NC group. The Pre-group had more highly expanded T cell clones compared to Post1, Post7 and NC groups, and the diversity of the T cell repertoire of the Post7 group was significantly decreased compared to the Pre, Post1 and NC groups. In addition, we found our results also show that various TRBV expression increased and some public sequences at different time points after liver transplantation, and the expression levels of 3 TRBV segments and 2 TRBJ segments were also significantly different in Pre, Post1, Post7 and NC groups. Moreover, 1 aa sequence shared by all liver transplantation patients and 2 aa sequences shared by at least two groups, which may serve as biomarkers to monitor the immune status of liver transplant patients.
乙型肝炎肝硬化是一种免疫相关疾病，在此疾病中，肝细胞在机体免疫系统激活以清除病毒的过程中死亡，其进展与T淋巴细胞密切相关。T淋巴细胞通过膜蛋白T细胞受体（TCR），特别是通过主要组织相容性复合体（MHC）来识别抗原。在此，我们使用高通量免疫组库测序技术研究肝移植患者与健康对照（NC）之间TCR组库的特征和多样性。我们对6例肝移植患者移植前（Pre）、移植后第1天（Post1）和第7天（Post7）外周血单个核细胞（PBMC）中的TCRβ链互补决定区3（CDR3）组库进行了测序，同时也对6例NC进行了测序。我们观察到Pre、Post1、Post7和NC组之间CDR3、VD插入缺失和DJ插入缺失长度的分布相似。我们发现移植组的TCR组库多样性相较于NC组相对较低。与Post1、Post7和NC组相比，Pre组有更多高度扩增 的T细胞克隆，并且Post7组的T细胞组库多样性相较于Pre、Post1和NC组显著降低。此外，我们发现我们的结果还表明，肝移植后不同时间点各种TRBV表达增加且存在一些公共序列，并且3个TRBV区段和2个TRBJ区段的表达水平在Pre、Post1、Post7和NC组中也存在显著差异。此外，所有肝移植患者共享1个氨基酸序列，至少两组共享2个氨基酸序列，这些序列可能作为监测肝移植患者免疫状态 的生物标志物。
