Autoimmune diseases are defined as pathologies of adaptive immunity by the presence of autoantibodies or MHC-restricted autoantigen-reactive T cells. Because autoreactivity is a normal process based on mechanisms producing repertoires of antibodies and T cell receptors, crucial questions about disease mechanisms and key steps for interference have been outstanding. We defined 25 years ago the 'remnant epitopes generate autoimmunity' (REGA)-model in which extracellular proteases from innate immune cells generate autoantigens. Here, we refine the REGA-model, tested in diseases ranging from organ-specific autoimmune diseases to systemic lupus erythematosus. It now constitutes a paradigm in which remnant epitopes generate, maintain, and regulate autoimmunity; are dependent on genetic and epigenetic influences; are produced in a disease phase-specific manner; and have therapeutic implications when targeted.

中文翻译：

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产生自身免疫的残余表位：从模型到有用的范式。

自身免疫性疾病被定义为因自身抗体或 MHC 限制性自身抗原反应性 T 细胞的存在而产生的适应性免疫的病理学。由于自身反应性是基于抗体和 T 细胞受体产生机制的正常过程，因此有关疾病机制和干扰关键步骤的关键问题一直悬而未决。25 年前，我们定义了“残余表位产生自身免疫”(REGA) 模型，其中先天免疫细胞的胞外蛋白酶产生自身抗原。在这里，我们改进了 REGA 模型，并在从器官特异性自身免疫性疾病到系统性红斑狼疮等疾病中进行了测试。它现在构成了残余表位生成、维持和调节自身免疫的范例；取决于遗传和表观遗传的影响；以特定于疾病阶段的方式产生；并在靶向时具有治疗意义。