AN ALTERED PEPTIDE LIGAND MEDIATES IMMUNE DEVIATION AND PREVENTS AUTOIMMUNE ENCEPHALOMYELITIS
AN ALTERED PEPTIDE LIGAND MEDIATES IMMUNE DEVIATION AND PREVENTS AUTOIMMUNE ENCEPHALOMYELITIS
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DOI：
10.1016/1074-7613(95)90169-8
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发表时间：
1995-10-01
期刊：
影响因子：
32.4
通讯作者：
KUCHROO, VK
中科院分区：
文献类型：
--
作者：
NICHOLSON, LB;GREER, JM;KUCHROO, VK
在由髓鞘蛋白脂质蛋白（PLP）肽139 - 151诱导的实验性自身免疫性脑脊髓炎（EAE）中，我们先前已表明该疾病由Th1细胞介导，这些细胞将色氨酸144识别为主要的T细胞受体（TCR）接触点。在此我们描述了一种改变的肽配体（APL），它是通过在144位（Q144）进行单个氨基酸替换（色氨酸替换为谷氨酰胺）而产生的，它能抑制由天然PLP 139 - 151肽（W144）诱导的EAE的发展。我们发现APL诱导的T细胞与天然肽具有交叉反应性，并且这些细胞产生Th2（白细胞介素 - 4和白细胞介素 - 10）以及Th0（干扰素γ和白细胞介素 - 10）细胞因子。用APL产生的T细胞系过继转移可预防EAE。这些数据表明，改变抗原肽中的单个氨基酸可显著影响T细胞分化，并提示免疫偏离可能是APL抑制自身免疫疾病的机制之一。
In experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, we have previously shown that the disease is mediated by Th1 cells, which recognize tryptophan 144 as the primary TCR contact point. Here we describe an altered peptide ligand (APL), generated by a single amino acid substitution (tryptophan to glutamine) at position 144 (Q144), which inhibits the development of EAE induced with the native PLP 139-151 peptide (W144). We show that the APL induces T cells that are cross-reactive with the native peptide and that these cells produce Th2 (IL-4 and IL-10) and Th0 (IFN gamma and IL-10) cytokines. Adoptive transfer of T cell lines generated with the APL confer protection from EAE. These data show that changing a single amino acid in an antigenic peptide can significantly influence T cell differentiation and suggest that immune deviation may be one of the mechanisms by which APLs can inhibit an autoimmune disease.