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多发性硬化症患者来源的髓鞘碱性蛋白特异性T细胞克隆的优先肽特异性和HLA限制

Preferential peptide specificity and HLA restriction of myelin basic protein-specific T cell clones derived from MS patients.

作者信息

Zhang J W, Chou C H, Hashim G, Medaer R, Raus J C

机构信息

Department of Immunology, Dr. L. Willems Instituut, Universitaire campus, Diepenbeek, Belgium.

出版信息

Cell Immunol. 1990 Aug;129(1):189-98. doi: 10.1016/0008-8749(90)90197-y.

DOI:10.1016/0008-8749(90)90197-y
PMID:1694729
Abstract

A panel of 17 myelin basic protein (MBP)-specific T lymphocyte clones were generated from four multiple sclerosis (MS) patients. All T cell clones expressed CD4 phenotype and 14 clones exhibited substantial cytotoxic activity on MBP-coated target cells. T cell recognition sites of the clones on human MBP were identified by using MBP fragments and synthetic peptides. Despite the fact that at least three epitopes were defined, these T cell clones displayed a striking bias to the C-terminal peptide 149-171 independent of differences in HLA-DR and DQ expression. In addition, the T cell responses of the clones appeared to be restricted by HLA-DR molecules irrespective of peptide specificities. The present study suggests an immunodominant property of the C-terminal peptide for HLA-DR-restricted T cell responses to MBP. However, its association with encephalitogenicity in humans and its potential pathologic importance in MS await further clarification.

摘要

从4例多发性硬化症(MS)患者中产生了一组17个髓鞘碱性蛋白(MBP)特异性T淋巴细胞克隆。所有T细胞克隆均表达CD4表型,14个克隆对包被MBP的靶细胞表现出显著的细胞毒性活性。通过使用MBP片段和合成肽确定了这些克隆在人MBP上的T细胞识别位点。尽管确定了至少三个表位,但这些T细胞克隆对C末端肽149 - 171表现出显著的偏向性,且与HLA - DR和DQ表达的差异无关。此外,无论肽的特异性如何,这些克隆的T细胞反应似乎都受HLA - DR分子的限制。本研究提示C末端肽对于HLA - DR限制的T细胞对MBP的反应具有免疫显性特性。然而,其与人类致脑炎性的关联及其在MS中的潜在病理学重要性仍有待进一步阐明。

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