Peptide-specific prevention of experimental allergic encephalomyelitis. Neonatal tolerance induced to the dominant T cell determinant of myelin basic protein.
Peptide-specific prevention of experimental allergic encephalomyelitis. Neonatal tolerance induced to the dominant T cell determinant of myelin basic protein.
复制标题
实验过敏性脑脊髓炎的肽特异性预防。新生儿耐受性诱导的髓磷脂碱性蛋白的主要T细胞决定因素。
DOI：
10.1084/jem.169.5.1681
复制
发表时间：
1989-05-01
影响因子：
15.3
通讯作者：
Sercarz, E E
中科院分区：
文献类型：
--
作者：
Clayton, J P;Gammon, G M;Ando, D G;Kono, D H;Hood, L;Sercarz, E E
实验性变态反应性脑脊髓炎(EAE)是一种抗原特异性T细胞介导的自身免疫性疾病模型。髓鞘碱性蛋白(MBP)NH2末端的9个氨基酸(1-9NAc)是诱导B10.PL(H-2U)株EAE的主要T细胞表位。我们对新生B10.PL小鼠耐受1-9NAc，并研究了该多肽和整个MBP的增殖反应。在新生期暴露于1-9NAc的小鼠在增殖T细胞水平上对随后的攻击具有耐受性。同样，在1-9NAc耐受组中，1-9NAc诱导的EAE的发生率和严重程度都显著降低。事实上，我们能够耐受对MBP正常反应的小鼠，这表明这种自身抗原是隔离的(在中枢神经系统内)，因此通常不会诱导对它的耐受。在对照组动物和耐受1-9NAc的小鼠(两组均为50%)中，对大鼠MBP的反应的发病率没有显著差异，这表明至少在分子的其他地方存在一个额外的脑源性决定因素。我们已经成功地通过多肽诱导的耐受来预防疾病诱导。多肽诱导耐受为预防自身免疫提供了一种新的、特异的策略。然而，显然有必要充分定义所有可能诱导致病T细胞的表位，以确保完全有效地治疗T细胞介导的自身免疫性疾病。
Experimental allergic encephalomyelitis (EAE) is a model of antigen- specific T cell-mediated autoimmune disease. The alpha-acetylated, NH2- terminal nine amino acids (1-9NAc) of myelin basic protein (MBP) represents the dominant T cell epitope for the induction of EAE in the B10.PL (H-2u) strain. We tolerized neonatal B10.PL mice to 1-9NAc and studied the proliferative responses to this peptide and to whole MBP. Mice exposed to 1-9NAc in the neonatal period were tolerant to subsequent challenge at the proliferative T cell level. Similarly, in the 1-9NAc-tolerant group, both the incidence and severity of 1-9NAc induced EAE were greatly reduced. The fact that we were able to tolerize mice normally responsive to MBP suggests that this self antigen is sequestered (within the central nervous system) and hence tolerance to it is not normally induced. No significant difference in disease incidence was seen in response to rat MBP between control animals and 1-9NAc-tolerized mice (50% in both groups), demonstrating the presence of at least one additional encephalitogenic determinant elsewhere on the molecule. We have successfully prevented disease induction by peptide-induced tolerization. Tolerance induction by peptides provides a new and specific strategy in the prevention of autoimmunity. However, it will be clearly necessary to fully define all epitopes potentially capable of inducing pathogenic T cells to ensure complete and effective therapy of T cell-mediated autoimmune disease.