Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Eur J Immunol. 2021 Apr;51(4):835-847. doi: 10.1002/eji.202048961. Epub 2021 Feb 10.
Autophagy has been reported to be involved in supporting antigen cross-presentation by dendritic cells (DCs). We have shown that DCs have the ability to store antigen for a prolonged time in endolysosomal compartments and thereby sustain MHCI antigen cross-presentation to CD8 T cells. In the current study, we investigated the role of autophagy in long-term antigen presentation. We show that the autophagy machinery has a negative impact on storage of antigen in DCs. Atg5 DCs which are deficient in autophagy or DCs treated with common autophagy inhibitors showed enhanced antigen storage and antigen cross-presentation. This augmented antigen cross-presentation effect is independent of altered proteasome enzyme activity or MHCI surface expression on DCs. We visualized that the storage compartments are in close proximity to LC3 positive autophagosomes. Our results indicate that autophagosomes disrupt antigen storage in DCs and thereby regulate long-term MHCI cross-presentation.
自噬被报道参与支持树突状细胞（DC）的抗原交叉呈递。我们已经表明，DC 具有将抗原在内溶酶体隔室中长时间储存的能力，从而维持 MHCI 抗原对 CD8 T 细胞的交叉呈递。在本研究中，我们研究了自噬在长期抗原呈递中的作用。我们表明，自噬机制对 DC 中抗原的储存有负面影响。缺乏自噬的 Atg5 DC 或用常见自噬抑制剂处理的 DC 显示出增强的抗原储存和抗原交叉呈递。这种增强的抗原交叉呈递效应与蛋白酶体酶活性或 DC 表面 MHCI 表达的改变无关。我们观察到，储存隔室与 LC3 阳性自噬体密切相关。我们的结果表明，自噬体破坏 DC 中的抗原储存，从而调节长期 MHCI 交叉呈递。
