Baleeiro Renato B, Walden Peter
Charité-Universitätsmedizin Berlin, Department of Dermatology, Venerology and Allergology, Clinical Research Group Tumour Immunology, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Department of Dermatology, Venerology and Allergology, Clinical Research Group Tumour Immunology, Berlin, Germany.
Mol Immunol. 2017 Aug;88:148-154. doi: 10.1016/j.molimm.2017.06.028. Epub 2017 Jun 20.
Cross-presentation of endocytosed antigen is essential for induction of CD8 effector T cell responses and a hallmark of dendritic cells (DCs). The mode of antigen processing in this context is controversial and some models imply translocation of the antigen from the endosomes into the cytosol. To test this hypothesis we made use of the pro-apoptotic properties of cytochrome c when in the cytosol, and confirmed that it indeed triggered apoptosis of human immature DCs but only at high concentrations. Proteasome inhibitors reduced the required concentration of cytochrome c thousand-fold, indicating that protein translocated into the cytosol is rapidly degraded by proteasomes. Mature DCs were also susceptible to cytochrome c-triggered apoptosis at high concentrations but proteasome inhibitors did not increase their sensitivity. Other cross-presenting cells such as B cells and monocytes were not sensitive to cytochrome c at all, indicating that they do not shuttle internalized antigen into the cytosol. Thus, processing of internalized antigens seems to follow different pathways depending on cell type and, in case of DCs, maturation state. Immature DCs appear to have a unique capacity to shuttle external antigen into the cytosol for proteasomal processing, which could explain their efficiency in antigen cross-presentation.
内吞抗原的交叉呈递对于诱导CD8效应T细胞反应至关重要，是树突状细胞（DC）的一个标志。在这种情况下，抗原加工的模式存在争议，一些模型暗示抗原从内体转运到细胞质中。为了验证这一假设，我们利用了细胞色素c在细胞质中时的促凋亡特性，并证实它确实能触发人未成熟DC的凋亡，但仅在高浓度时。蛋白酶体抑制剂将细胞色素c所需浓度降低了千倍，表明转运到细胞质中的蛋白质会被蛋白酶体迅速降解。成熟DC在高浓度时也易受细胞色素c触发的凋亡影响，但蛋白酶体抑制剂并未增加其敏感性。其他交叉呈递细胞，如B细胞和单核细胞，对细胞色素c完全不敏感，表明它们不会将内化抗原转运到细胞质中。因此，内化抗原的加工似乎因细胞类型而异，对于DC来说，还取决于成熟状态。未成熟DC似乎具有将外部抗原转运到细胞质中进行蛋白酶体加工的独特能力，这可以解释它们在抗原交叉呈递中的效率。
