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HLA DR2(15)+ 多发性硬化症中对髓鞘少突胶质细胞糖蛋白肽的反应性增加及表位作图

Increased reactivity to myelin oligodendrocyte glycoprotein peptides and epitope mapping in HLA DR2(15)+ multiple sclerosis.

作者信息

Wallström E, Khademi M, Andersson M, Weissert R, Linington C, Olsson T

机构信息

Neuroimmunology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.

出版信息

Eur J Immunol. 1998 Oct;28(10):3329-35. doi: 10.1002/(SICI)1521-4141(199810)28:10<3329::AID-IMMU3329>3.0.CO;2-B.

DOI:10.1002/(SICI)1521-4141(199810)28:10<3329::AID-IMMU3329>3.0.CO;2-B
PMID:9808202
Abstract

Multiple sclerosis (MS) is a central nervous system-specific inflammatory and demyelinating disease where a myelin-directed autoimmune response is thought to be pathogenetically relevant. Myelin oligodendrocyte glycoprotein (MOG) is a surface-exposed minor myelin component that is a prime candidate autoantigen. We have investigated peripheral blood lymphocyte responses to synthetic 15-26 amino acids long overlapping MOG peptides in 20 MS patients and 14 healthy controls with the MS-associated HLA haplotype DR2(15). There were significantly increased responses, in terms of numbers of cells secreting IFN-gamma detected by Elispot in response to several MOG-derived peptides in the MS patients, but not the healthy controls. MOG peptide 63-87 evoked the strongest response, and the stimulatory property of this peptide was confirmed in additional DR2(15)+ MS patients where a peptide concentration-dependent proliferative response, which was inhibited by the addition of anti-HLA class II antibodies, was observed. This is the first work detailing putative immunodominant T cell epitopes of MOG in DR2(15)+ MS patients.

摘要

多发性硬化症(MS)是一种中枢神经系统特异性炎症性脱髓鞘疾病,其中针对髓鞘的自身免疫反应被认为与发病机制相关。髓鞘少突胶质细胞糖蛋白(MOG)是一种暴露于表面的次要髓鞘成分,是主要的自身抗原候选物。我们研究了20例MS患者和14例具有MS相关HLA单倍型DR2(15)的健康对照者外周血淋巴细胞对合成的15 - 26个氨基酸长的重叠MOG肽的反应。通过酶联免疫斑点法检测,MS患者对几种MOG衍生肽产生分泌γ干扰素的细胞数量反应显著增加,而健康对照者则无此现象。MOG肽63 - 87引发的反应最强,在另外的DR2(15)+ MS患者中证实了该肽的刺激特性,观察到其呈肽浓度依赖性增殖反应,且添加抗HLA II类抗体可抑制该反应。这是第一项详细描述DR2(15)+ MS患者中MOG假定免疫显性T细胞表位的研究。

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