Stevens D B, Chen K, Seitz R S, Sercarz E E, Bronstein J M
Department of Neurology and the Brain Research Institute, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
J Immunol. 1999 Jun 15;162(12):7501-9.
Oligodendrocyte-specific protein (OSP) is a recently isolated and cloned, 207-aa, hydrophobic, four-transmembrane protein found in CNS myelin. It represents approximately 7% of total myelin protein. The OSP cDNA sequence has no significant homology with previously reported genes, but the predicted protein structure suggests that OSP is a CNS homologue of peripheral myelin protein-22. We previously reported the presence of anti-OSP Abs in the cerebrospinal fluid of relapsing-remitting multiple sclerosis (MS) patients, but not control patient groups. In this study, we tested the ability of a panel of 20-mer peptides with 10-aa overlaps, representing the sequence of murine OSP, to induce experimental autoimmune encephalomyelitis (EAE), an animal model for MS. SJL mice challenged with murine OSP peptides 52-71, 82-101, 102-121, 142-161, 182-201, and 192-207 exhibited clinical EAE. OSP:52-71 elicited severe relapsing-remitting EAE in some individuals. All other encephalitogenic peptides elicited, at most, a loss of tail tonicity from which the mice most often completely recovered. Mononuclear cell infiltrates and focal demyelination characteristic of EAE were evident. T cell proliferative responses were seen with all encephalitogenic peptides except 142-161 and 182-201. OSP peptides 72-91 and 132-151 did not cause clinical EAE, but did elicit robust proliferative responses. B10.PL and PL/J mice challenged with the same OSP peptide doses as SJL mice did not exhibit clinical EAE. These results in the SJL EAE model, together with the results from MS patient clinical samples, make OSP a promising candidate for autoantigenic involvement in MS.
少突胶质细胞特异性蛋白（OSP）是一种最近分离和克隆的、含207个氨基酸的疏水四跨膜蛋白，存在于中枢神经系统髓鞘中。它约占髓鞘蛋白总量的7%。OSP的cDNA序列与先前报道的基因无显著同源性，但预测的蛋白质结构表明OSP是外周髓鞘蛋白-22的中枢神经系统同源物。我们先前报道复发缓解型多发性硬化症（MS）患者的脑脊液中存在抗OSP抗体，而对照组患者中则没有。在本研究中，我们测试了一组代表鼠OSP序列、有10个氨基酸重叠的20肽诱导实验性自身免疫性脑脊髓炎（EAE）的能力，EAE是MS的动物模型。用鼠OSP肽52 - 71、82 - 101、102 - 121、142 - 161、182 - 201和192 - 207攻击的SJL小鼠出现了临床EAE。OSP:52 - 71在一些个体中引发了严重的复发缓解型EAE。所有其他致脑炎性肽最多只引起尾部张力丧失，小鼠大多能完全恢复。EAE特征性的单核细胞浸润和局灶性脱髓鞘明显。除142 - 161和182 - 201外，所有致脑炎性肽都能引起T细胞增殖反应。OSP肽72 - 91和132 - 151未引起临床EAE，但能引发强烈的增殖反应。用与SJL小鼠相同剂量的OSP肽攻击的B10.PL和PL/J小鼠未出现临床EAE。SJL EAE模型中的这些结果，连同MS患者临床样本的结果，使OSP成为MS自身抗原参与的一个有前景的候选物。
