AMINO-ACID HOMOLOGY BETWEEN THE ENCEPHALITOGENIC SITE OF MYELIN BASIC-PROTEIN AND VIRUS - MECHANISM FOR AUTOIMMUNITY
AMINO-ACID HOMOLOGY BETWEEN THE ENCEPHALITOGENIC SITE OF MYELIN BASIC-PROTEIN AND VIRUS - MECHANISM FOR AUTOIMMUNITY
复制标题
DOI：
10.1126/science.2414848
复制
发表时间：
1985-01-01
期刊：
影响因子：
56.9
通讯作者：
OLDSTONE, MBA
中科院分区：
文献类型：
--
作者：
FUJINAMI, RS;OLDSTONE, MBA
在病毒和宿主致脑炎蛋白之间发现了氨基酸序列同源性。然后利用与自身蛋白发生交叉反应的病毒肽在兔子体内引发免疫反应。在用病毒肽免疫的动物的中枢神经系统中观察到单核细胞浸润。髓鞘碱性蛋白（MBP）是一种宿主蛋白，其由10个氨基酸组成的致脑炎位点可诱发实验性过敏性脑脊髓炎。通过计算机分析，发现乙型肝炎病毒聚合酶（HBVP）与兔MBP的致脑炎位点有6个连续的氨基酸相同。给兔子注射从HBVP中选取的8个或10个氨基酸的肽段后，兔子产生的抗体既能与HBVP的预定序列反应，也能与天然MBP反应。来自免疫兔子的外周血单核细胞在与MBP或HBVP一起孵育时会增殖。从这些兔子身上获取的中枢神经系统组织呈现出类似实验性过敏性脑脊髓炎的组织学图像。因此，病毒感染可能通过一种被称为分子模拟的机制触发产生与自身蛋白发生交叉反应的抗体和单核细胞。在引发免疫反应的感染性病毒不存在的情况下，由此产生的自身过敏事件也可能导致组织损伤。
Amino acid sequence homology was found between viral and host encephalitogenic protein. Immune responses were then generated in rabbits by using the viral peptide that cross-reacts with the self-protein. Mononuclear cell infiltration was observed in the central nervous systems of animals immunized with the viral peptide. Myelin basic protein (MBP) is a host protein whose encephalitogenic site of ten amino acids induces experiemtnal allergic encephalomyelitis. By computer analysis, hepatitis B virus polymerase (HBVP) was found to share six consecutive amino acids with the encephalitogenic site of rabbit MBP. Rabbits given injections of a selected eight- or ten-amino acid peptide from HBVP made antibody that reacted with the predetermined sequences of HBVP and also with native MBP. Peripheral blood mononuclear cells from the immunized rabbits proliferated when incubated with either MBP or HBVP. Central nervous system tissue taken from these rabbits had a histologic picture reminiscent of experimental allergic encephalomyelitis. Thus, viral infection may trigger the production of antibodies and mononuclear cells that cross-react with self-proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoallergic event can take place in the absence of the infectious virus that initiated the immune response.