T-cell receptor (TCR) usage in Lewis rat experimental autoimmune encephalomyelitis: TCR beta-chain-variable-region V beta 8.2-positive T cells are not essential for induction and course of disease.
T-cell receptor (TCR) usage in Lewis rat experimental autoimmune encephalomyelitis: TCR beta-chain-variable-region V beta 8.2-positive T cells are not essential for induction and course of disease.
复制标题
T 细胞受体 (TCR) 在 Lewis 大鼠实验性自身免疫性脑脊髓炎中的应用：TCR β 链可变区 V β 8.2 阳性 T 细胞对于疾病的诱导和病程并不是必需的。
DOI：
10.1073/pnas.92.13.5850
复制
发表时间：
1995
影响因子：
11.1
通讯作者：
K. Toyka
中科院分区：
文献类型：
--
作者：
R. Gold;G. Giegerich;H. Hartung;K. Toyka
据报道，对髓鞘碱性蛋白(MBP)有反应的致病Lewis大鼠T细胞主要使用编码T细胞受体(TCR)β链可变区的Vβ8.2基因片段。然而，在一组MBP特异性T细胞系中，高达75%的α/βT细胞不显示TCR Vβ8.2、Vβ8.5、Vβ10或Vβ16元件。为了进一步研究TCR的使用情况，我们对Vβ8.2和Vβ10阳性的T细胞系进行了分类，或耗尽了含有这些TCR的细胞系。Vβ8.2阳性T细胞和其中一个耗尽的T细胞株与MBP多肽MBP-(68-88)发生强烈反应。耗尽的T细胞系可导致显著的实验性自身免疫性脑脊髓炎(EAE)，即使在Lewis大鼠中，内源性Vβ8.2阳性T细胞已被抗Vβ8.2单抗治疗消除。从该品系产生的T细胞杂交瘤主要使用Vβ3 TCR基因与TCR Vα2转录本共表达，Vβ8.2阳性T细胞也使用这些转录本。此外，对MBP-(44-67)反应的Vβ10阳性T细胞在阳性选择后立即注射是脑源性的。在分选的Vβ8.2或Vβ10阳性T细胞株诱导EAE后，脊髓组织的免疫细胞化学分析显示，注射的TCR或在注射耗竭的T细胞系后的不可分型的α/βT细胞占优势。我们的结果表明，在近交系中，即使对于单一的自身抗原，TCRβ链的使用也是不同的。此外，Vβ8.2阳性T细胞对于过继转移性EAE的诱导和进展不是必需的。
Predominant usage of V beta 8.2 gene segments, encoding a T-cell receptor (TCR) beta chain variable region, has been reported for pathogenic Lewis rat T cells reactive to myelin basic protein (MBP). However, up to 75% of the alpha/beta T cells in a panel of MBP-specific T-cell lines did not display TCR V beta 8.2, V beta 8.5, V beta 10, or V beta 16 elements. To further investigate TCR usage, we sorted the T-cell lines for V beta 8.2- and V beta 10-positive T cells or depleted the lines of cells with these TCRs. V beta 8.2-positive T cells and one of the depleted T-cell lines strongly reacted against the MBP peptide MBP-(68-88). The depleted T-cell line caused marked experimental autoimmune encephalomyelitis (EAE) even in Lewis rats in which endogenous V beta 8.2-positive T cells had been eliminated by neonatal treatment with anti-V beta 8.2 monoclonal antibodies. T-cell hybridomas generated from this line predominantly used V beta 3 TCR genes coexpressed with TCR V alpha 2 transcripts, which were also used by V beta 8.2-positive T cells. Furthermore, V beta 10-positive T cells reactive to MBP-(44-67) were encephalitogenic when injected immediately after positive selection. After induction of EAE by sorted V beta 8.2- or V beta 10-positive T-cell lines, immunocytochemical analysis of the spinal cord tissue showed a predominance of the injected TCR or of nontypable alpha/beta T cells after injection of the depleted line. Our results demonstrate heterogeneity of TCR beta-chain usage even for a single autoantigen in an inbred strain. Moreover, V beta 8.2-positive T cells are not essential for the induction and progression of adoptive-transfer EAE.