Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease.
Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease.
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DOI：
10.1172/jci.insight.144869
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发表时间：
2021-02-22
期刊：
影响因子：
8
通讯作者：
Jacobson S
中科院分区：
文献类型：
--
作者：
Nozuma S;Enose-Akahata Y;Johnson KR;Monaco MC;Ngouth N;Elkahloun A;Ohayon J;Zhu J;Jacobson S
在这项研究中，我们检查和特点的疾病特异性TCR签名在脑脊液（CSF）与HTLV-1相关的脊髓病/热带痉挛性轻瘫（HAM/TSP）的患者。使用基于独特分子识别符的方法，对来自HAM/TSP患者和正常健康供体（ND）的配对外周血单核细胞（PBMC）和CSF细胞中的TCR β库进行测序。序列分析表明，HAM/TSP患者CSF中的TCR β谱系高度扩增，并且包含与PBMC共享的TCR克隆型和在CSF中独特富集的TCR克隆型。此外，我们分析了来自HLA-A*0201+ HAM/TSP的PBMC的高度扩增和潜在免疫病理性HTLV-1 Tax 11 -19特异性CD 8 + T细胞的TCR β库，并在CDR 3区鉴定了保守基序（PGLAG）。重要的是，HTLV-1 Tax 11 -19特异性CD 8 + T细胞中扩增克隆的TCR β克隆型也在同一患者的CSF中扩增和富集。这些结果表明，探索CSF和抗原特异性T细胞的TCR库可以在病毒相关神经系统疾病中提供TCR库签名。
In this study, we examined and characterized disease-specific TCR signatures in cerebrospinal fluid (CSF) of patients with HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). TCR β libraries using unique molecular identifier–based methodologies were sequenced in paired peripheral blood mononuclear cells (PBMCs) and CSF cells from HAM/TSP patients and normal healthy donors (NDs). The sequence analysis demonstrated that TCR β repertoires in CSF of HAM/TSP patients were highly expanded and contained both TCR clonotypes shared with PBMCs and uniquely enriched within the CSF. In addition, we analyzed TCR β repertoires of highly expanded and potentially immunopathologic HTLV-1 Tax11-19–specific CD8+ T cells from PBMCs of HLA-A*0201+ HAM/TSP and identified a conserved motif (PGLAG) in the CDR3 region. Importantly, TCR β clonotypes of expanded clones in HTLV-1 Tax11-19–specific CD8+ T cells were also expanded and enriched in the CSF of the same patient. These results suggest that exploring TCR repertoires of CSF and antigen-specific T cells may provide a TCR repertoire signature in virus-associated neurologic disorders.