Ribosomal versus non-ribosomal cellular antigens: factors determining efficiency of indirect presentation to CD4+ T cells.
Ribosomal versus non-ribosomal cellular antigens: factors determining efficiency of indirect presentation to CD4+ T cells.
复制标题
核糖体与非核糖体细胞抗原：决定间接呈递至 CD4 T 细胞的效率的因素。
DOI：
10.1111/j.1365-2567.2010.03258.x
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发表时间：
2010
期刊：
影响因子：
6.4
通讯作者：
Schreiber,Hans
中科院分区：
文献类型：
--
作者：
Philip,Mary;Schietinger,Andrea;Schreiber,Hans
死亡细胞释放的蛋白质可以被抗原提呈细胞(APC)摄取并呈递给T细胞。虽然这种自身抗原的呈递可能会导致有益的抗肿瘤反应，但在自身免疫性疾病中，它会导致病理性免疫反应。自身免疫性疾病靶向的自身蛋白质亚集是有限的，某些细胞成分，如核糖核蛋白(RNP)复合体经常是靶标。虽然已经提出了对这种抗原选择性的解释，但几乎没有对这些假说进行直接测试。我们和其他人之前表明，核糖体蛋白是自身免疫性疾病的靶标，也是抗肿瘤T细胞反应的靶标。我们询问核糖体蛋白的特殊性质，如掺入RNP复合体或亚细胞定位，是否能通过APC增强核糖体蛋白向CD4+T细胞的呈递。APC同样很好地吸收和呈递了纯化的完整核糖体内或不含核糖体的核糖体蛋白抗原，表明将核糖体蛋白包含在RNP复合体中并不具有优势。然而，定位于凋亡细胞内核糖体的抗原在APC中的摄取和呈递效率低于弥漫在整个细胞中的相同抗原。这表明核糖体蛋白的表达在某种程度上被下调，可能是为了促进其他不那么丰富的细胞内蛋白的表达。因此，自身免疫和抗肿瘤T细胞反应经常以核糖体蛋白为靶点的解释不是从凋亡细胞摄取的水平上的，必须从其他地方寻找。
Proteins released from dying cells can be taken up and presented by antigen‐presenting cells (APC) to T cells. While the presentation of such self antigens may lead to beneficial anti‐tumour responses, in autoimmune disease it leads to pathological immune responses. The sub‐set of self proteins targeted in autoimmune disease is circumscribed, and certain cellular components such as ribonucleoprotein (RNP) complexes are often targeted. Although explanations for this antigen selectivity have been proposed, there has been little direct testing of these hypotheses. We and others previously showed that ribosomal proteins, targeted in autoimmune disease, are also targets of anti‐tumour T‐cell responses. We asked whether particular properties of ribosomal proteins such as incorporation into RNP complexes or sub‐cellular localization enhance ribosomal protein presentation by APC to CD4+T cells. Ribosomal protein antigens within purified intact ribosomes or free of the ribosomes were equally well taken up and presented by APC, demonstrating that inclusion of ribosomal proteins into an RNP complex does not confer an advantage. However, antigens localized to ribosomes within apoptotic cells were less efficiently taken up and presented by APC than the same antigens localized diffusely throughout the cell. This suggests that presentation of ribosomal proteins is somehow down‐regulated, possibly to facilitate presentation of other less‐abundant intracellular proteins. Consequently, the explanation for the frequent targeting of ribosomal proteins by both autoimmune and anti‐tumour T‐cell responses is not at the level of uptake from apoptotic cells and must be sought elsewhere.