A functional and structural basis for TCR cross-reactivity in multiple sclerosis
A functional and structural basis for TCR cross-reactivity in multiple sclerosis
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DOI：
10.1038/ni835
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发表时间：
2002-10-01
影响因子：
30.5
通讯作者：
Fugger, L
中科院分区：
文献类型：
--
作者：
Lang, HLE;Jacobsen, H;Fugger, L
多发性硬化（MS）相关的HLA主要组织相容性复合体（MHC）II类等位基因DRB 1 *1501，DRB 5 *0101和DQB 1 *0602处于强烈的连锁不平衡，使得难以确定哪一个是主要的MS风险基因。在这里，我们表明，DRB 1和DRB 5基因座一起可能会影响MS的易感性。我们证明，从MS患者的T细胞受体（TCR）承认DRB 1 *1501限制性髓鞘碱性蛋白（MBP）和DRB 5 *0101限制性EB病毒（EBV）肽。DRB 5 *0101-EBV肽复合物的晶体结构测定揭示了在用于TCR识别的表面处与DRB 1 *1501-MBP肽复合物的显著程度的结构等效性。这为涉及HLA分子的分子模拟提供了结构证据。结构的细节表明，在HLA相关疾病的优势MHC II类协会的解释。
The multiple sclerosis (MS)-associated HLA major histocompatibility complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong linkage disequilibrium, making it difficult to determine which is the principal MS risk gene. Here we show that together the DRB1 and DRB5 loci may influence susceptibility to MS. We demonstrate that a T cell receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV peptide complex revealed a marked degree of structural equivalence to the DRB1*1501-MBP peptide complex at the surface presented for TCR recognition. This provides structural evidence for molecular mimicry involving HLA molecules. The structural details suggest an explanation for the preponderance of MHC class II associations in HLA-associated diseases.