Differential use of autophagy by primary dendritic cells specialized in cross-presentation

Antigen-presenting cells survey their environment and present captured antigens bound to major histocompatibility complex (MHC) molecules. Formation of MHC-antigen complexes occurs in specialized compartments where multiple protein trafficking routes, still incompletely understood, converge. Autophagy is a route that enables the presentation of cytosolic antigen by MHC class II molecules. Some reports also implicate autophagy in the presentation of extracellular, endocytosed antigen by MHC class I molecules, a pathway termed “cross-presentation.” The role of autophagy in cross-presentation is controversial. This may be due to studies using different types of antigen presenting cells for which the use of autophagy is not well defined. Here we report that active use of autophagy is evident only in DC subtypes specialized in cross-presentation. However, the contribution of autophagy to cross-presentation varied depending on the form of antigen: it was negligible in the case of cell-associated antigen or antigen delivered via receptor-mediated endocytosis, but more prominent when the antigen was a soluble protein. These findings highlight the differential use of autophagy and its machinery by primary cells equipped with specific immune function, and prompt careful reassessment of the participation of this endocytic pathway in antigen cross-presentation.

抗原呈递细胞（Antigen-presenting cells）可监测其所处微环境，并将捕获的抗原与主要组织相容性复合体（major histocompatibility complex, MHC）分子结合后呈递。MHC-抗原复合物的形成发生于特化的胞内区室中，多条尚未完全阐明的蛋白质运输通路在此汇聚。
自噬（autophagy）是一条介导MHC II类分子呈递胞质抗原的通路。部分研究还证实自噬参与了MHC I类分子对胞外内吞抗原的呈递过程，该通路被命名为“交叉呈递（cross-presentation）”。自噬在交叉呈递中的作用尚存争议，这或许是因为相关研究所使用的抗原呈递细胞类型各异，且这类细胞对自噬的利用方式尚未明确界定。
本研究发现，仅在专司交叉呈递的树突状细胞（dendritic cells, DC）亚型中，可观测到细胞对自噬的活跃利用。但自噬对交叉呈递的贡献因抗原形式而异：对于细胞结合型抗原或经受体介导内吞递送的抗原，自噬的贡献微乎其微；而当抗原为可溶性蛋白时，自噬的作用则更为显著。
上述研究结果凸显了具备特定免疫功能的原代细胞对自噬及其相关机制的差异化利用，并提示需审慎重新评估该内吞通路在抗原交叉呈递中的参与作用。