The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat
The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat
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DOI：
10.1016/0165-5728(95)00124-7
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发表时间：
1995-12-01
影响因子：
3.3
通讯作者：
Dornmair, K
中科院分区：
文献类型：
--
作者：
Adelmann, M;Wood, J;Dornmair, K
利用高度纯化的重组蛋白mMOG，我们证明了对髓鞘少突胶质细胞糖蛋白（MOG） n端结构域（a.a 1-125）的自身免疫反应可诱导Lewis大鼠实验性自身免疫性脑脊髓炎（EAE）的急性脱髓鞘变异。用100 μ g的mMOG佐剂接种尾尾后，11只动物中有9只出现轻度临床疾病（平均临床评分1.1）。该疾病在组织病理学上表现为中枢神经系统（CNS）存在炎症和局灶性脱髓鞘病变。过继性转移实验表明，这种炎症性脱髓鞘病理是由弱脑源性、mog特异性T细胞反应和脱髓鞘之间的协同作用介导的；mog特异性自身抗体反应。使用体外选择的mmog反应性T细胞系，发现对MOG这一结构域的脑致生T细胞反应识别两个不同的表位，MOG（1-20）和MOG(35-55)；而ELISA检测结果显示免疫优势B细胞表位位于氨基酸序列MOG（1-25）内。然而，尽管与T细胞表位MOG（1-20）或MOG（35-55）相对应的合成肽的主动免疫诱导了中枢神经系统的炎症反应，但这与脱髓鞘无关，这表明脱髓鞘抗体反应识别其他可能依赖构象的表位。本研究明确表明，MOG特异性自身免疫反应本身足以诱导中枢神经系统脱髓鞘疾病，并支持MOG可能在多发性硬化症的免疫发病机制中发挥重要作用的建议。
Using a highly purified recombinant protein, mMOG, we demonstrate that autoimmune responses to the N-terminal domain (a.a. 1-125) of the myelin oligodendrocyte glycoprotein (MOG) induce an acute demyelinating variant of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Immunisation with 100 mu g of mMOG in adjuvant at the base of the tail induced mild clinical disease in 9 of 11 animals (mean clinical score 1.1). The disease was characterised histopathologically by the presence of inflammation and focal demyelinating lesions in the central nervous system (CNS). Adoptive transfer experiments suggest that this inflammatory demyelinating pathology is mediated by synergy between a weakly encephalitogenic, MOG-specific T cell response and a demyelinating; MOG-specific autoantibody response. Using in vitro selected mMOG-reactive T cell lines, the encephalitogenic T cell response to this domain of MOG was found to recognise two distinct epitopes, MOG(1-20) and MOG(35-55); whereas ELISA demonstrated that the immunodominant B cell epitope was located within the amino acid sequence MOG(1-25). However although active immunisation with synthetic peptides corresponding to the T cell epitopes, MOG(1-20) or MOG(35-55), induced an inflammatory response in the CNS, this was not associated with demyelination indicating that the demyelinating antibody response recognises other, possibly conformation dependent epitopes. This study unequivocally demonstrates that MOG-specific autoimmune responses are alone sufficient to induce a demyelinating disease of the CNS and supports the proposal that MOG may play an important role in the immunopathogenesis of multiple sclerosis.