Analysis of pathomechanism of autommune encephalomyelitis and development of new therapeutic strategies.

1)实验性sutoimmune encepha lomelitis （EAE）动物微透析血清素无明显差异。2)髓鞘碱性蛋白（MBP）肽89-101特异性脑源性T克隆的T细胞受体分析显示，V β的使用多种多样，但在CDR3区有一定的保守序列。3)合成脑源性T细胞克隆利用的V β 17a CDR 2肽诱导双阴性抑制因子，在体内有效抑制EAE。4)注射活化的脑源性T细胞克隆诱导抗麦角型抑制因子。建立了识别抗麦角型抗原的单克隆抗体，并开始了cDNA的克隆。5) HSP65在少突胶质细胞中的表达。6)多发性硬化症（MS）患者外周血淋巴细胞对MBP89-101或蛋白脂质蛋白（PLP） 85-169的应答频率较高，推测了PLP的免疫优势区。PLP肽特异性T细胞克隆利用了多种B β s，但在CDR3区域发现了一些有趣的序列。这些结果表明，利用T细胞受体肽和麦角型抗原可以建立新的治疗EAE的策略，这适用于人类疾病MS。

1) Microdialysis of animals with experimental sutoimmune encepha lomyelitis (EAE) did not show difference in serotonin.2) Analysis of T cell receptors of myelin basic protein (MBP) peptide 89-101-specific encephalitogenic T clones revealed diverse V beta usage but certain conserved sequences in the CDR3 region.3) Synthetic peptide of V beta 17a CDR 2 which is utilized by encephalitogenic T cell clones induced double negative suppressors which effectively suppressed EAE in vivo.4) Injection of activated encephalitogenic T cell clones induced antiergotype suppressors. Monoclonal antibodies which recognize the antiergotype antigen were established, and we started cloning of the cDNA.5) We have shown the expression of HSP65 on oligodendrocytes.6) Higher frequency of lymphocytes responding to MBP89-101 or proteolipid protein (PLP) 85-169 was shown in peripheral blood of multiple sclerosis (MS) patients, and immunodominant regions of PLP were speculated. PLP peptide-specific T cell clones utilized diverse B beta s but certain interesting sequences were found in the CDR3 region. These results suggest that new strategies for therapy of EAE can be established by using peptides of T cell receptors and ergotype antigens and this is applicable to human disease MS.