Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes.
Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes.
复制标题
通过多发性硬化症患者的自身抗体和 HLA-DR2 限制性 T 细胞克隆识别免疫显性髓磷脂碱性蛋白肽。
DOI：
10.1172/jci119622
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Warren,KG
中科院分区：
文献类型：
--
作者：
Wucherpfennig,KW;Catz,I;Hausmann,S;Strominger,JL;Steinman,L;Warren,KG
髓鞘碱性蛋白(MBP)可能是多发性硬化症(MS)的重要自身抗原，MBP(82-100)区是T细胞和自身抗体的免疫优势区。将自身抗体识别的结构要求与先前为MBP特异性T细胞克隆定义的结构要求进行了比较。MBP自身抗体是从11/12例死后研究的中枢神经系统病变中亲和纯化的。MBP(83-97)肽抑制自身抗体与MBP和GT；95%的结合，因此在所有11例病例中均为免疫优势。有助于自身抗体结合的残基位于10个氨基酸片段(V86-T95)，该片段还包含T细胞表位的MHC/T细胞受体接触残基。在表位中心，相同的残基对于抗体结合和T细胞识别是重要的。根据抗体结合基序，鉴定出与纯化的自身抗体结合的微生物多肽。与微生物多肽的自身抗体结合需要在表位中心的四个或五个连续残基上具有序列一致性。以前发现的激活T细胞克隆的微生物多肽与MBP没有如此明显的同源性，因为MHC接触处不要求序列相同。B细胞和T细胞具有相似的优良特异性，可能有助于诱导MS患者对MBP的耐受。
Myelin basic protein (MBP) may be an important autoantigen in multiple sclerosis (MS), with the MBP(82-100) region being immunodominant for T cells and autoantibodies. The structural requirements for autoantibody recognition were compared to those previously defined for MBP-specific T cell clones. MBP autoantibodies were affinity-purified from central nervous system lesions of 11/12 postmortem cases studied. The MBP(83-97) peptide was immunodominant in all 11 cases since it inhibited autoantibody binding to MBP > 95%. Residues contributing to autoantibody binding were located in a 10-amino acid segment (V86-T95) that also contained the MHC/T cell receptor contact residues of the T cell epitope. In the epitope center, the same residues were important for antibody binding and T cell recognition. Based on the antibody-binding motif, microbial peptides were identified that were bound by purified autoantibodies. Autoantibody binding of microbial peptides required sequence identity at four or five contiguous residues in the epitope center. Microbial peptides previously found to activate T cell clones did not have such obvious homology to MBP since sequence identity was not required at MHC contacts. The similar fine specificity of B cells and T cells may be useful for tolerance induction to MBP in MS.