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由针对髓鞘蛋白脂蛋白合成肽的克隆T细胞介导的实验性变应性脑脊髓炎。精细特异性和T细胞受体Vβ使用情况。

Experimental allergic encephalomyelitis mediated by cloned T cells specific for a synthetic peptide of myelin proteolipid protein. Fine specificity and T cell receptor V beta usage.

作者信息

Kuchroo V K, Sobel R A, Laning J C, Martin C A, Greenfield E, Dorf M E, Lees M B

机构信息

Department of Pathology, Harvard Medical School, Boston, MA 02115.

出版信息

J Immunol. 1992 Jun 15;148(12):3776-82.

PMID:1376341
Abstract

Proteolipid protein (PLP) is the major protein of central nervous system myelin. SJL (H-2s) mice immunized with a synthetic peptide corresponding to PLP residues 139-151 develop acute EAE. In this study, 6 IAs-restricted, CD4+, TCR alpha beta-bearing T cell clones were derived from SJL/J mice after immunization with this synthetic peptide. The clones responded in in vitro proliferative assays to the whole PLP molecule and to PLP peptide 139-151, but not to irrelevant Ag. They also responded to truncated and overlapping forms of the peptide but five distinct reactivity patterns were observed using these peptides. A panel of anti-TCR V beta mAb and TCR V beta-specific cDNA probes were used to determine the TCR V beta usage of the clones. Five clones were found to use four different V beta (V beta 2, V beta 6, V beta 10, or V beta 17a), whereas the V beta on the sixth clone could not be identified. Five of the clones induced EAE of varying severity upon adoptive transfer into naive syngeneic mice or mice pretreated with irradiation and pertussis and one clone was nonencephalitogenic. The Ag-specific proliferative response of all but the nonencephalitogenic clone could be blocked by an anti-CD4 mAb. Thus, the clones showed differences in their fine specifity, TCR V beta usage, sensitivity to antibody blocking, and encephalitogenic potency. These data demonstrate that the T cell response to the encephalitogenic PLP peptide 139-151 is heterogeneous.

摘要

蛋白脂蛋白(PLP)是中枢神经系统髓磷脂的主要蛋白质。用与PLP第139 - 151位残基对应的合成肽免疫的SJL(H - 2s)小鼠会发生急性实验性自身免疫性脑脊髓炎(EAE)。在本研究中,用这种合成肽免疫SJL/J小鼠后,从其体内获得了6个受I - A抗原限制、CD4 +、表达TCRαβ的T细胞克隆。这些克隆在体外增殖试验中对完整的PLP分子和PLP肽139 - 151有反应,但对无关抗原无反应。它们也对该肽的截短和重叠形式有反应,但使用这些肽观察到了五种不同的反应模式。使用一组抗TCR Vβ单克隆抗体和TCR Vβ特异性cDNA探针来确定克隆的TCR Vβ使用情况。发现5个克隆使用四种不同的Vβ(Vβ2、Vβ6、Vβ10或Vβ17a),而第六个克隆的Vβ无法鉴定。将其中5个克隆过继转移到同基因的未致敏小鼠或经照射和百日咳预处理的小鼠体内后,会诱发不同严重程度的EAE,有一个克隆不具有致脑炎性。除了不具有致脑炎性的克隆外,所有克隆的抗原特异性增殖反应都可被抗CD4单克隆抗体阻断。因此,这些克隆在精细特异性、TCR Vβ使用情况、对抗体阻断的敏感性和致脑炎性效力方面存在差异。这些数据表明,T细胞对致脑炎性PLP肽139 - 151的反应是异质性的。

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