Granzyme B cleavage of autoantigens in autoimmunity.
Granzyme B cleavage of autoantigens in autoimmunity.
复制标题
自身免疫中自动抗原的谷物酶B裂解。
DOI：
10.1038/cdd.2009.197
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发表时间：
2010-04
影响因子：
12.4
通讯作者：
Rosen A
中科院分区：
文献类型：
--
作者：
Darrah E;Rosen A
系统性自身免疫性疾病是一组复杂的疾病，其特征在于高滴度自身抗体的产生和免疫介导的组织损伤。自身免疫性风湿病的两个显著特征是它们的自我维持性质和自我扩增能力，例如疾病爆发。这些特征表明疾病传播中存在前馈循环，其中免疫效应物途径驱动自身抗原的产生/释放，这反过来又促进免疫应答。越来越多的人认识到，在细胞毒性颗粒诱导的细胞死亡过程中，结构修饰是自身抗原的一个常见和显著的特征，并且可能是驱动疾病的一个重要原则。本文综述了颗粒酶B（GrB）介导的自身抗原切割，包括自身抗原中GrB切割位点的特征，自身抗原切割位点与自身抗原表位的共定位，以及自身抗原在疾病相关靶组织中的GrB敏感性。GrB诱导的自身抗原结构的变化可能有助于自身免疫的启动和传播的机制进行了审查，并揭示GrB有可能创建或破坏自身免疫表位。由于仍然没有直接的证据表明GrB切割抗原在产生自身免疫的因果关系的作用，本次审查突出了重要的悬而未决的问题GrB在自身抗原选择的作用。
The systemic autoimmune diseases are a complex group of disorders characterized by elaboration of high titer autoantibodies and immune-mediated damage of tissues. Two striking features of autoimmune rheumatic diseases are their self-sustaining nature and capacity for auto-amplification, exemplified by disease flares. These features suggest the presence of a feed-forward cycle in disease propagation, in which immune effector pathways drive the generation/release of autoantigens, which in turn fuel the immune response. There is a growing awareness that structural modification during cytotoxic granule-induced cell death is a frequent and striking feature of autoantigens, and may be an important principle driving disease. This review focuses on granzyme B (GrB)-mediated cleavage of autoantigens including (i) features of GrB cleavage sites within autoantigens, (ii) co-location of cleavage sites with autoimmune epitopes, and (iii) GrB-sensitivity of autoantigens in disease-relevant target tissue. The mechanisms whereby GrB-induced changes in autoantigen structure may contribute to the initiation and propagation of autoimmunity are reviewed and reveal that GrB has the potential to create or destroy autoimmune epitopes. As there remains no direct evidence demonstrating a causal role for GrB-cleavage of antigens in the generation of autoimmunity, this review highlights important outstanding questions about the role of GrB in autoantigen selection.
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影响因子：
15.9
作者：
Goebels, N;Michaelis, D;Hohlfeld, R
通讯作者：
Hohlfeld, R
影响因子：
4.8
作者：
Adrain, C;Murphy, BM;Martin, SJ
通讯作者：
Martin, SJ
影响因子：
3.7
作者：
Beyer, TD;Kolowos, W;Herrmann, M
通讯作者：
Herrmann, M
DOI：
10.1161/01.atv.0000147162.51930.b7
发表时间：
2004-12-01
影响因子：
8.7
作者：
Choy, JC;Hung, VHY;Granville, DJ
通讯作者：
Granville, DJ
DOI：
10.1084/jem.181.5.1863
发表时间：
1995-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bender A;Ernst N;Iglesias A;Dornmair K;Wekerle H;Hohlfeld R
通讯作者：
Hohlfeld R