Shamshiev A, Donda A, Carena I, Mori L, Kappos L, De Libero G
Department of Research, University Hospital Basel, Switzerland.
Eur J Immunol. 1999 May;29(5):1667-75. doi: 10.1002/(SICI)1521-4141(199905)29:05<1667::AID-IMMU1667>3.0.CO;2-U.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by discrete areas of demyelination. An autoimmune response against components of myelin is thought to contribute to disease pathogenesis. Here we identify glycolipids as new targets recognized by T cells in multiple sclerosis patients. Circulating T cells reactive with glycolipids are more frequent in MS patients than in control donors as shown by enzyme-linked immunospot assay. They specifically recognize different types of glycolipids, such as gangliosides, sulfatide and galactosylceramide and release IFN-gamma and TNF-alpha. T cells specific for gangliosides were found to be CD8+, TCR alphabeta+, restricted by the MHC-like CD1b molecule and specific for epitopes residing in the carbohydrate moiety of gangliosides. Our findings suggest that in addition to self proteins, self glycolipids may represent potential source of autoantigens recognized by T cells in autoimmune diseases.
多发性硬化症（MS）是一种中枢神经系统的慢性炎症性疾病，其特征为离散的脱髓鞘区域。针对髓鞘成分的自身免疫反应被认为与疾病发病机制有关。在此，我们确定糖脂是多发性硬化症患者中T细胞识别的新靶点。酶联免疫斑点试验表明，与糖脂反应的循环T细胞在MS患者中比在对照供体中更常见。它们特异性识别不同类型的糖脂，如神经节苷脂、硫脂和半乳糖基神经酰胺，并释放γ干扰素和肿瘤坏死因子-α。发现对神经节苷脂特异的T细胞为CD8 +、TCR αβ +，受MHC样CD1b分子限制，且对位于神经节苷脂碳水化合物部分的表位特异。我们的研究结果表明，除自身蛋白质外，自身糖脂可能是自身免疫疾病中T细胞识别的自身抗原的潜在来源。
