Department of Cell Biology and Neurosciences, Section of Experimental Immunotherapy, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy;
Blood. 2012 Feb 9;119(6):1407-17. doi: 10.1182/blood-2011-06-363564. Epub 2011 Dec 19.
Cross-presentation allows antigen-presenting cells to present exogenous antigens to CD8(+) T cells, playing an essential role in controlling infections and tumor development. IFN-α induces the rapid differentiation of human mono-cytes into dendritic cells, known as IFN-DCs, highly efficient in mediating cross-presentation, as well as the cross-priming of CD8(+) T cells. Here, we have investigated the mechanisms underlying the cross-presentation ability of IFN-DCs by studying the intracellular sorting of soluble ovalbumin and nonstructural-3 protein of hepatitis C virus. Our results demonstrate that, independently from the route and mechanism of antigen entry, IFN-DCs are extraordinarily competent in preserving internalized proteins from early degradation and in routing antigens toward the MHC class-I processing pathway, allowing long-lasting, cross-priming capacity. In IFN-DCs, both early and recycling endosomes function as key compartments for the storage of both antigens and MHC-class I molecules and for proteasome- and transporter-associated with Ag processing-dependent auxiliary cross-presentation pathways. Because IFN-DCs closely resemble human DCs naturally occurring in vivo in response to infections and other danger signals, these findings may have important implications for the design of vaccination strategies in neoplastic or chronic infectious diseases.
交叉呈递使抗原呈递细胞能够将外源性抗原呈递给 CD8(+)T 细胞，在控制感染和肿瘤发展方面发挥着重要作用。IFN-α诱导人单核细胞迅速分化为树突状细胞，称为 IFN-DC，其在介导交叉呈递以及 CD8(+)T 细胞的交叉启动方面非常有效。在这里，我们通过研究可溶性卵清蛋白和丙型肝炎病毒非结构-3 蛋白的细胞内分拣，研究了 IFN-DC 交叉呈递能力的机制。我们的结果表明，无论抗原进入的途径和机制如何，IFN-DC 都非常擅长从早期降解中保护内化的蛋白质，并将抗原定向 MHC Ⅰ类加工途径，从而允许长期的交叉启动能力。在 IFN-DC 中，早期和再循环内体都作为储存抗原和 MHC Ⅰ类分子的关键隔室，并作为蛋白酶体和与 Ag 处理相关的转运体依赖的辅助交叉呈递途径发挥作用。由于 IFN-DC 非常类似于体内感染和其他危险信号诱导的天然存在的人 DC，这些发现可能对肿瘤或慢性感染性疾病的疫苗接种策略的设计具有重要意义。
