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

Composition and variation analysis of the TCR β-chain CDR3 repertoire in systemic lupus erythematosus using high-throughput sequencing
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DOI:
10.1016/j.molimm.2015.07.012
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发表时间:
2015-10-01
影响因子:
3.6
通讯作者:
Dai, Yong
Dai, Yong
中科院分区:
医学3区
文献类型:
--
作者:
Sui, Weiguo;Hou, Xianliang;Dai, Yong

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T淋巴细胞针对多种病原体发起免疫应答的能力主要由T细胞受体(TCR)的高变互补决定区3(CDR 3)区段的氨基酸(aa)序列传达。在这项研究中,我们使用多重PCR,Illumina测序和IMGT/HighV-QUEST的组合,对SLE患者和健康供体(NC)外周血单核细胞(PBMC)中T细胞受体BV互补决定区3(TCR BV CDR 3)基因的特征和多态性进行标准化分析。我们发现CDR 3、VD插入缺失和DJ插入缺失长度的分布在SLE和NC组之间是相当的。SLE组的克隆扩增程度明显大于NC组,10个TR β V片段和6个TR β J片段的表达水平在SLE组也有显著性差异。关于公共T细胞应答,3CDR 3 DNA序列和4aa序列为所有SLE患者所共有,并且可作为SLE疾病风险、诊断和/或预后的生物标志物。(C)2015爱思唯尔有限公司版权所有。
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 TR beta V segments and 6 TR beta J 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. (C) 2015 Elsevier Ltd. All rights reserved.