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T细胞受体Vβ基因亚家族在自身免疫性脑脊髓炎中的优势表达

Predominant expression of a T cell receptor V beta gene subfamily in autoimmune encephalomyelitis.

作者信息

Zamvil S S, Mitchell D J, Lee N E, Moore A C, Waldor M K, Sakai K, Rothbard J B, McDevitt H O, Steinman L, Acha-Orbea H

机构信息

Department of Neurology, Stanford University, California 94305.

出版信息

J Exp Med. 1988 May 1;167(5):1586-96. doi: 10.1084/jem.167.5.1586.

Abstract

TCR beta chain gene expression of individual T cell clones that share the same MHC class II restriction and similar fine specificity for the encephalitogenic NH2 terminus of the autoantigen myelin basic protein (MBP) has been examined. TCR V beta expression was examined by FACS analysis with mAbs specific for the V beta 8 subfamily of TCR beta chain genes. 14 of 18 (78%) NH2-terminal MBP-specific clones examined express a member of the TCR V beta 8 subfamily. Southern analysis was used to identify which member(s) of the TCR V beta 8 subfamily is expressed by these clones. Each of four clones examined uses V beta 8.2, though two different V beta 8.2-J beta 2 combinations were identified. Our findings indicate that there is restricted TCR V beta usage in the autoimmune T cell response to the dominant encephalitogenic NH2-terminal epitope of the MBP. The use of an mAb to the antigen-specific TCR in the prevention of T cell-mediated autoimmune disease has been investigated. Our results demonstrate that in vivo administration of a TCR V beta 8-specific mAb prevents induction of autoimmune encephalomyelitis.

摘要

对具有相同II类主要组织相容性复合体(MHC)限制性且对自身抗原髓鞘碱性蛋白(MBP)的致脑炎NH2末端具有相似精细特异性的单个T细胞克隆的TCRβ链基因表达进行了检测。通过使用针对TCRβ链基因Vβ8亚家族的单克隆抗体(mAb)进行荧光激活细胞分选(FACS)分析来检测TCR Vβ表达。在检测的18个NH2末端MBP特异性克隆中,有14个(78%)表达TCR Vβ8亚家族的一个成员。采用Southern分析来确定这些克隆表达的是TCR Vβ8亚家族的哪个成员。所检测的四个克隆均使用Vβ8.2,不过鉴定出了两种不同的Vβ8.2-Jβ2组合。我们的研究结果表明,在针对MBP主要致脑炎NH2末端表位的自身免疫性T细胞应答中,TCR Vβ的使用是受限的。已对使用针对抗原特异性TCR的mAb预防T细胞介导的自身免疫性疾病进行了研究。我们的结果表明,在体内给予TCR Vβ8特异性mAb可预防自身免疫性脑脊髓炎的诱导。

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