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利用高通量测序技术对系统性红斑狼疮中TCR β链CDR3库进行组成及变异分析

Composition and variation analysis of the TCR β-chain CDR3 repertoire in systemic lupus erythematosus using high-throughput sequencing.

作者信息

Sui Weiguo, Hou Xianliang, Zou Guimian, Che Wenti, Yang Ming, Zheng Can, Liu Fuhua, Chen Peng, Wei Xiaolian, Lai Liusheng, Dai Yong

机构信息

Nephrology Department of Guilin 181st Hospital, Guangxi Key laboratory of Metabolic Diseases Research, 541002 Guilin, Guangxi, China.

College of Life Science, Guangxi Normal University, 541004 Guilin, Guangxi, China.

出版信息

Mol Immunol. 2015 Oct;67(2 Pt B):455-64. doi: 10.1016/j.molimm.2015.07.012. Epub 2015 Jul 27.

DOI:10.1016/j.molimm.2015.07.012
PMID:26227771
Abstract

The ability of T lymphocytes to mount an immune response against a diverse array of pathogens is primarily conveyed by the amino acid (aa) sequence of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (TCR). In this study, we used a combination of multiplex-PCR, Illumina sequencing and IMGT/HighV-QUEST for a standardized analysis of the characteristics and polymorphisms of the T-cell receptor BV complementarity-determining region 3 (TCR BV CDR3) gene in peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy donors (NC). We found the distributions of CDR3, VD indel, and DJ indel lengths to be comparable between the SLE and NC groups. The degree of clonal expansion in the SLE group was significantly greater than in the NC group, and the expression levels of 10 TRβV segments and 6 TRβJ segments were also significantly different in the SLE group. Regarding public T cell responses, 3CDR3 DNA sequences and 4 aa sequences were shared by all SLE patients and may serve as biomarkers for SLE disease risk, diagnosis and/or prognosis.

摘要

T淋巴细胞针对多种病原体发起免疫反应的能力主要由T细胞受体(TCR)的高变互补决定区3(CDR3)片段的氨基酸(aa)序列传递。在本研究中,我们联合使用多重PCR、Illumina测序和IMGT/HighV-QUEST对系统性红斑狼疮(SLE)患者和健康对照(NC)外周血单个核细胞(PBMC)中T细胞受体BV互补决定区3(TCR BV CDR3)基因的特征和多态性进行标准化分析。我们发现SLE组和NC组之间CDR3、VD插入缺失和DJ插入缺失长度的分布具有可比性。SLE组的克隆扩增程度显著高于NC组,并且SLE组中10个TRβV片段和6个TRβJ片段的表达水平也存在显著差异。关于公共T细胞反应,所有SLE患者共有3个CDR3 DNA序列和4个aa序列,它们可能作为SLE疾病风险、诊断和/或预后的生物标志物。

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