Section of Immunobiology, Department of Ophthalmology, University Hospital, LMU Munich, München, Germany.
Front Immunol. 2020 Oct 29;11:580636. doi: 10.3389/fimmu.2020.580636. eCollection 2020.
Molecular or antigenic mimicry is a term for the similarity of different antigens, which can be confused by the immune system. Antigen recognition by antibodies and T cell receptors is specific, but not restricted to a single antigen. Both types of receptors specifically recognize antigens and are expressed with a very high but still restricted variability compared to the number of different antigens they potentially could bind. T cell receptors only can bind to antigen peptides presented on certain self-MHC-molecules by screening only some amino acid side chains on both the presented peptides and the MHC molecule. The other amino acids of the peptide are not directly perceived by the T cell, offering the opportunity for a single T cell to recognize a variety of different antigens with the same receptor, which significantly increases the immune repertoire. The immune system is usually tolerant to autoantigens, especially to those of immune privileged sites, like the eye. Therefore, autoimmune diseases targeting these organs were hard to explain, unless a T cell is activated by an environmental peptide (e.g. pathogen) that is similar, but not necessarily identical with an autoantigen. Here we describe antigenic mimicry of retinal autoantigens with a variety of non-ocular antigens resulting in the induction of intraocular inflammation. T cells that are activated by mimotopes outside of the eye can pass the blood-retina barrier and enter ocular tissues. When reactivated in the eye by crossreaction with autoantigens they induce uveitis by recruiting inflammatory cells.
分子或抗原模拟是指不同抗原之间的相似性，这可能会被免疫系统混淆。抗体和 T 细胞受体对抗原的识别是特异性的，但并不局限于单一抗原。这两种受体都特异性地识别抗原，并且与它们潜在结合的不同抗原数量相比，表达具有非常高但仍然有限的可变性。T 细胞受体只能通过筛选呈递肽和 MHC 分子上的某些氨基酸侧链，结合在某些自身 MHC 分子上呈递的抗原肽。肽的其他氨基酸不会被 T 细胞直接感知，这为单个 T 细胞提供了用相同受体识别多种不同抗原的机会，这显著增加了免疫库。免疫系统通常对自身抗原耐受，特别是对免疫特权部位的自身抗原耐受，如眼睛。因此，针对这些器官的自身免疫性疾病很难解释，除非 T 细胞被与自身抗原相似但不一定相同的环境肽（例如病原体）激活。在这里，我们描述了视网膜自身抗原与多种非眼部抗原的抗原模拟，导致眼内炎症的发生。在眼外被模拟表位激活的 T 细胞可以穿过血视网膜屏障并进入眼部组织。当它们与自身抗原发生交叉反应而在眼中被重新激活时，通过招募炎症细胞引起葡萄膜炎。
