Autoantigenesis: the evolution of protein modifications in autoimmune disease.

Autoantigenesis: the evolution of protein modifications in autoimmune disease.
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DOI:
10.1016/j.coi.2011.12.003
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发表时间:
2012-02
影响因子:
7
通讯作者:
Mamula MJ
Mamula MJ
中科院分区:
医学2区
文献类型:
--
作者:
Doyle HA;Mamula MJ

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自身免疫性疾病中的蛋白质靶标有不同的位置,如SLE一样,起源于细胞内,或存在于细胞表面或细胞外空间。“自体反生”一词在这里首先被定义为当自身蛋白质打破自身耐受性并触发自身免疫B和/或T细胞反应时发生的变化。正如许多研究表明的那样,人体内50%到90%的蛋白质获得翻译后修饰。在某些情况下,这些修饰可能对于它们所在细胞的蛋白质的生物学功能或作为细胞外介质是必要的。综上所述,很明显,一些翻译后修饰可以通过改变免疫处理和递呈来产生新的自身抗原。虽然存在许多蛋白质修饰,但我们将重点介绍那些在炎症或其他免疫系统反应中创建、放大或改变的修饰。最后,我们将讨论自身抗原的翻译后修饰如何影响B和T细胞特异性的分析、当前的诊断技术和/或自身免疫性疾病的免疫疗法的发展。
Protein targets in autoimmune disease vary in location, originating within cells as in SLE, or found on cell surfaces or in extracellular spaces. The term “autoantigenesis” is first defined here as the changes that arise in self-proteins as they break self tolerance and trigger autoimmune B and/or T cell responses. As illustrated in many studies, between 50 and 90% of the proteins in the human body acquire posttranslational modification. In some cases, it may be that these modifications are necessary for the biological functions of proteins of the cells in which they reside or as extracellular mediators. Summarized herein, it is clear that some posttranslational modifications can create new self-antigens by altering immunologic processing and presentation. While many protein modifications exist, we will focus on those created, amplified, or altered in the context of inflammation or other immune system responses. Finally, we will address how posttranslational modifications in self-antigens may affect the analyses of B and T cell specificity, current diagnostic techniques, and/or the development of immunotherapies for autoimmune diseases.
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