An exclusive feature of dendritic cells (DCs) is their capacity to present exogenous antigens by MHC class I molecules, called cross-presentation. Here, we show that protein antigen can be conserved in mature murine DCs for several days in a lysosome-like storage compartment, distinct from MHC class II and early endosomal compartments, as an internal source for the supply of MHC class I ligands. Using two different uptake routes via Fcγ receptors and C-type lectin receptors, we could show that antigens were routed towards the same endolysosomal compartments after 48 h. The antigen-containing compartments lacked co-expression of molecules involved in MHC class I processing and presentation including TAP and proteasome subunits as shown by single-cell imaging flow cytometry. Moreover, we observed the absence of cathepsin S but selective co-localization of active cathepsin X with protein antigen in the storage compartments. This indicates cathepsin S-independent antigen degradation and a novel but yet undefined role for cathepsin X in antigen processing and cross-presentation by DCs. In summary, our data suggest that these antigen-containing compartments in DCs can conserve protein antigens from different uptake routes and contribute to long-lasting antigen cross-presentation.

中文翻译：

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不同的抗原摄取受体路由到相同的存储隔间以在树突细胞中交叉呈递

树突状细胞 (DC) 的一个独特特征是它们通过 MHC I 类分子呈递外源抗原的能力，称为交叉呈递。在这里，我们展示了蛋白质抗原可以在成熟的鼠 DCs 中在溶酶体样储存室中保存几天，不同于 MHC II 类和早期内体室，作为 MHC I 类配体供应的内部来源。通过 Fcγ 受体和 C 型凝集素受体使用两种不同的摄取途径，我们可以证明抗原在 48 小时后被路由到相同的内溶酶体区室。如单细胞成像流式细胞术所示，含抗原的隔室缺乏参与 MHC I 类加工和呈递的分子的共表达，包括 TAP 和蛋白酶体亚基。而且，我们观察到组织蛋白酶 S 不存在，但活性组织蛋白酶 X 与蛋白质抗原在储存室中选择性共定位。这表明组织蛋白酶 S 独立的抗原降解和组织蛋白酶 X 在抗原加工和 DC 交叉呈递中的新但尚未确定的作用。总之，我们的数据表明 DC 中这些含有抗原的隔室可以保护来自不同摄取途径的蛋白质抗原，并有助于长期持续的抗原交叉呈递。