Barnett L A, Fujinami R S
Department of Neurology, University of Utah, Salt Lake City 84132.
FASEB J. 1992 Feb 1;6(3):840-4. doi: 10.1096/fasebj.6.3.1740233.
Many mechanisms may account for immune-mediated pathology after viral infections. Although several means have been hypothesized to play a role in disease, a widely accepted mechanism for viral-induced autoimmunity is molecular mimicry. It is thought that damage could result from an immune response to similar regions shared between virus and the host. Using computer-aided analysis, many sequence homologies have been identified between virus and host antigens. Using peptides corresponding to these regions, immunologic cross-reactivity has been found. In some cases, monoclonal antibodies to peptides of these regions have been shown to directly induce or augment disease in animal models. Using this approach to identify similar regions, it is possible to associate a known autoantigen with an infectious agent in autoimmune diseases in which there is no known etiologic agent. Conversely, it would also be possible to associate a known viral constituent with an unknown host antigen. Furthermore, identification of disease-inducing regions of autoantigens or viral proteins may lead to immunotherapeutic approaches to establish tolerance or anergy to such disease-inducing regions.
病毒感染后,许多机制可能导致免疫介导的病理变化。尽管已有多种假说认为某些因素在疾病中发挥作用,但病毒诱导自身免疫的一个广泛接受的机制是分子模拟。据认为,对病毒与宿主之间共享的相似区域的免疫反应可能导致损伤。通过计算机辅助分析,已在病毒和宿主抗原之间鉴定出许多序列同源性。使用与这些区域对应的肽段,已发现免疫交叉反应性。在某些情况下,针对这些区域肽段的单克隆抗体已被证明可在动物模型中直接诱导或加剧疾病。利用这种方法鉴定相似区域,有可能在病因不明的自身免疫性疾病中将已知自身抗原与感染因子联系起来。相反,也有可能将已知病毒成分与未知宿主抗原联系起来。此外,鉴定自身抗原或病毒蛋白的致病区域可能会带来免疫治疗方法,以建立对此类致病区域的耐受性或无反应性。