How can cryptic epitopes trigger autoimmunity?
How can cryptic epitopes trigger autoimmunity?
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神秘的表位如何触发自身免疫性？
DOI：
10.1084/jem.181.6.1945
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发表时间：
1995-06-01
影响因子：
15.3
通讯作者：
Lanzavecchia, A
中科院分区：
文献类型：
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作者：
Lanzavecchia, A
T细胞的耐受性依赖于自身蛋白对T细胞的呈递，因此只能对那些在稳态条件下产生的足以被胸腺缺失或外周无能的T细胞识别的自主决定因素建立。因此，有大量的自我决定因素是隐晦的，因为它们根本不是产生的，或者是在亚阈值水平产生的。这些隐蔽表位的特异性T细胞存在于正常的表位库中，如果这些表位以较高的浓度呈现，可能会被激活和自我攻击。这个概念最初是由Sercarz和他的同事提出的，它代表了今天关于自身免疫性疾病发病机制的主要假说。根本的问题是，通常是隐蔽的表位如何变得对免疫系统可见，并引发持续的致病反应。本期《实验医学杂志》上的两篇报告描述了两种可能负责揭示神秘决定因素的新机制。将这一新信息与以前的报告放在一起，试图描绘出不同的机制如何协同诱导、发展和维持自身免疫反应是很有吸引力的。
T cell tolerance depends on the presentation of selfproteins to T cells and therefore can only be established to those self-determinants which, under steady-state conditions, are generated in sufficient amounts to be recognized by T cells undergoing deletion in thymus or anergy in the periphery. Thus, there is large number of self-determinants that are cryptic because they are not generated at all or are generated at subthreshold levels. T cells specific for these cryptic epitopes are present in the normal repertoire and might become activated and autoaggressive if the epitopes are presented at higher concentrations. This concept, which had been originally proposed by Sercarz and colleagues, represents today the major hypothesis for the pathogenesis of autoimmune diseases (1). The fundamental question is how epitopes that are normally cryptic may become visible to the immune system and elicit a sustained pathogenetic response. Two reports in this issue of The Journal of Experimental Medicine describe two novel mechanisms that may be responsible for revealing cryptic determinants. It is tempting to put this new information together with previous reports to try to delineate how different mechanisms may synergize for the induction, development, and maintenance of an autoimmune response.