Persistent expression of experimental autoimmune encephalomyelitis (EAE)-specific Vbeta8.2 TCR spectratype in the central nervous system of rats with chronic relapsing EAE.

Persistent expression of experimental autoimmune encephalomyelitis (EAE)-specific Vbeta8.2 TCR spectratype in the central nervous system of rats with chronic relapsing EAE.
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慢性复发性 EAE 大鼠中枢神经系统中实验性自身免疫性脑脊髓炎 (EAE) 特异性 Vbeta8.2 TCR 谱型的持续表达。

DOI:
10.4049/jimmunol.161.12.6993
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发表时间:
1998
影响因子:
4.4
通讯作者:
Y. Matsumoto
Y. Matsumoto
中科院分区:
医学2区
文献类型:
--
作者:
G. Kim;K. Kohyama;N. Tanuma;H. Arimito;Y. Matsumoto

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监测TCR库对于评估T细胞相关自身免疫性疾病和随后的基于TCR的免疫治疗是必不可少的。在本研究中,我们通过CDR3谱分型检测了Lewis大鼠在脊髓匀浆免疫诱导的慢性复发性实验性自身免疫性脑脊髓炎(EAE)期间脊髓T细胞的TCR库。发现CDR3最短的Vbeta8.2谱型在整个病程中呈寡克隆扩增。此外,在EAE的第一次和第二次发作时观察到Vbeta12谱型扩展。序列分析显示,DSSYEQYF序列在Vbeta8.2家族中占优势群体,DSSYEQYF序列是髓鞘碱性蛋白(MBP)反应性T细胞克隆的代表序列。令人惊讶的是,Vbeta12也在CDR3区域使用了相同的氨基酸序列。这些发现表明,尽管中枢神经系统的浸润性T细胞被多克隆激活,但TCR库在整个过程中保持不变。此外,发现Vbeta8.2和Vbeta12谱型的主要CDR3氨基酸序列与MBP诱导的EAE相同,表明脊髓匀浆中单一的Ag(可能是MBP)参与了疾病的发展。
Monitoring the TCR repertoire is indispensable for the assessment of T cell-associated autoimmune diseases and subsequent TCR-based immunotherapy. In the present study, we examined the TCR repertoire of spinal cord T cells of Lewis rats by CDR3 spectratyping during chronic relapsing experimental autoimmune encephalomyelitis (EAE) induced by immunization with spinal cord homogenate. It was found that Vbeta8.2 spectratype with the shortest CDR3 expanded oligoclonally throughout the course of the disease. In addition, Vbeta12 spectratype expansion was observed at the first and second attacks of EAE. Sequence analysis revealed that clones with the DSSYEQYF sequence, which is a representative sequence of myelin basic protein (MBP)-reactive T cell clones, constituted the predominant population in the Vbeta8.2 family. Surprisingly, Vbeta12 also used the identical amino acid sequence in the CDR3 region. These findings indicate that although infiltrating T cells in the central nervous system are activated polyclonally, the TCR repertoire remains unchanged throughout the course. Moreover, the finding that the predominant CDR3 amino acid sequence of Vbeta8.2 and Vbeta12 spectratypes is identical with that of MBP-induced EAE suggests that a single Ag in spinal cord homogenate, possibly MBP, is involved in disease development.
与 Lewis 大鼠自身免疫性脑脊髓炎和碱性蛋白特异性 T 细胞克隆相关的 TCR V α CDR3 特异性基序。
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