THE SMALL HEAT-SHOCK PROTEIN ALPHA-B-CRYSTALLIN AS CANDIDATE AUTOANTIGEN IN MULTIPLE-SCLEROSIS
THE SMALL HEAT-SHOCK PROTEIN ALPHA-B-CRYSTALLIN AS CANDIDATE AUTOANTIGEN IN MULTIPLE-SCLEROSIS
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DOI：
10.1038/375798a0
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发表时间：
1995-06-29
期刊：
影响因子：
64.8
通讯作者：
RAVID, R
中科院分区：
文献类型：
--
作者：
VANNOORT, JM;VANSECHEL, AC;RAVID, R
人类自身免疫性疾病中关键抗原的鉴定是发展特异性干预的关键一步。与多发性硬化症（MS）相关的自身抗原可能存在于中枢神经系统的髓鞘中，即疾病的靶点（1）。在这里，我们研究了人类外周血T细胞的增殖反应的完整收集的髓鞘蛋白分馏的反相高效液相色谱。从MS受影响的大脑中分离的髓鞘含有单一的蛋白质组分，MS患者和健康对照组的T细胞对该蛋白质组分表现出显性反应。这种高度免疫原性的蛋白质被鉴定为α B-晶状体蛋白，一种小的热休克蛋白。免疫组化检查显示MS病变的少突胶质细胞和星形胶质细胞的存在与提高α B-晶体蛋白的表达，这是没有发现在未受影响的髓鞘。我们的研究结果表明，α B-晶状体蛋白作为免疫显性髓鞘抗原的人T细胞时，在活动性MS病变中发现的水平升高表达。
THE identification of key antigens in human autoimmune diseases is a crucial step towards the development of specific intervention. The autoantigen(s) relevant to multiple sclerosis (MS) probably reside in myelin of the central nervous system, the target of the disease(1). Here we examine proliferative responses of human peripheral blood T cells to the complete collection of myelin proteins fractionated by reversed-phase high-performance liquid chromatography. Myelin isolated from MS-affected brain contained a single protein fraction to which T cells from MS patients and from healthy controls showed dominant responses. This highly immunogenic protein was identified as alpha B-crystallin, a small heat-shock protein. Immunohistochemical examination of MS lesions revealed the presence of oligodendrocytes and astrocytes with raised alpha B- crystallin expression, which were not found in unaffected myelin. Our findings indicate that alpha B-crystallin serves as immunodominant myelin antigen to human T cells when expressed at the elevated levels found in active MS lesions.