Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein
Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein
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DOI：
10.1016/s1074-7613(00)80562-2
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发表时间：
1998-05-01
期刊：
影响因子：
32.4
通讯作者：
Goverman, J
中科院分区：
文献类型：
--
作者：
Harrington, CJ;Paez, A;Goverman, J
实验性变态反应性脑脊髓炎（EAE）是由T细胞介导的对中枢神经系统抗原的免疫诱导的。在H-2（U）小鼠中，EAE主要由髓鞘碱性蛋白（MBP）残基1-11特异性T细胞介导。我们证明，MBP 1 -11与MBP 121 -150中的表位的差异耐受性是由内源性MBP的表达诱导的，反映了肽/MHC复合物稳定性的极端差异。不同的MBP 121 -150特异性TCR库可分为三个精细的特异性组。尽管存在广泛的耐受性，但在野生型小鼠中鉴定出两组，但未检测到第三组。活化的MBP 121 -150特异性T细胞在野生型小鼠中诱导EAE。因此，逃避耐受性的致脑炎性T细胞要么识别短寿命的肽/MHC复合物，要么表达对稳定复合物具有独特特异性的TCR。
Experimental allergic encephalomyelitis (EAE) is induced by T cell-mediated immunity to central nervous system antigens. In H-2(U) mice, EAE is mediated primarily by T cells specific for residues 1-11 of myelin basic protein (MBP). We demonstrate that differential tolerance to MBP1-11 versus epitopes in MBP121-150 is induced by expression of endogenous MBP, reflecting extreme differences in stability of peptide/MHC complexes. The diverse MBP121-150-specific TCR repertoire can be divided into three fine specificity groups. Two groups were identified in wild-type mice despite extensive tolerance, but the third group was not detected. Activated MBP121-150-specific T cells induce EAE in wild-type mice. Thus, encephalitogenic T cells that escape tolerance either recognize short-lived peptide/MHC complexes or express TCRs with unique specificities for stable complexes.