Apoptosis of the teratocarcinoma cell line Tera-1 leads to the cleavage of HERV-K10gag proteins by caspases and/or granzyme B
Apoptosis of the teratocarcinoma cell line Tera-1 leads to the cleavage of HERV-K10gag proteins by caspases and/or granzyme B
复制标题
DOI：
10.1046/j.1365-3083.2002.01139.x
复制
发表时间：
2002-09-01
影响因子：
3.7
通讯作者：
Herrmann, M
中科院分区：
文献类型：
--
作者：
Beyer, TD;Kolowos, W;Herrmann, M
凋亡细胞衍生的自身抗原的免疫原性与其分布、翻译后修饰和与病毒抗原的共聚集有关。在系统性红斑狼疮（SLE）中，几乎所有已知的体液自身免疫反应的靶点在细胞凋亡期间都被半胱天冬酶或颗粒酶B切割。抗逆转录病毒蛋白的抗体可以经常检测到SLE患者血清中没有明显的逆转录病毒感染。这些抗体可能代表交叉反应性抗体，或者可能是由内源性逆转录病毒序列编码的蛋白质诱导的。我们使用Tera-1细胞，大量表达人类内源性逆转录病毒的组特异性抗原，HERV-K10（gag）多聚蛋白，研究其在细胞凋亡过程中的处理。与活细胞相比，诱导进行凋亡的Tera-1细胞显示出改变的HERV-K10（gag）加工。此外，颗粒酶B能够切割从活的Tera-1细胞分离的HERV-K10（gag）。这些翻译后修饰可能导致T细胞新表位的产生或逆转录病毒蛋白的表位层次的改变。因此，SLE患者中逆转录病毒抗原的免疫原性可能是由与核自身抗原相似的机制引起的。
Redistribution, post-translational modifications and coclustering with viral antigens contribute to the immunogenicity of apoptotic cell-derived autoantigens. Almost all known targets of the humoral autoimmune response in systemic lupus erythematosus (SLE) are cleaved by caspases or granzyme B during apoptosis. Antibodies against retroviral proteins can frequently be detected in the sera of SLE patients without overt retroviral infections. These antibodies may represent cross-reactive antibodies or may have been induced by proteins encoded by endogenous retroviral sequences. We used Tera-1 cells that abundantly express a group-specific antigen of human endogenous retroviruses, HERV-K10(gag) polyprotein, to investigate its processing during apoptosis. Tera-1 cells induced to undergo apoptosis showed an altered HERV-K10(gag) processing compared with viable cells. In addition, granzyme B was able to cleave HERV-K10(gag) isolated from viable Tera-1 cells.Similar to nuclear autoantigens, endogenous retroviral proteins are cleaved during the execution phase of apoptosis. These post-translational modifications may result in the generation of T-cell neoepitopes or a changed epitope hierarchy of retroviral proteins. Therefore, immunogenicity of retroviral antigens in SLE patients may result from a similar mechanism as described for nuclear autoantigens.