ABSTRACT

Dendritic cells (DC) have the unique capacity to activate naïve T cells by presenting T cell receptor specific peptides from exogenously acquired antigens bound to Major Histocompatibility Complex (MHC) molecules. MHC molecules are displayed on the DC plasma membrane as well as on extracellular vesicles (EV) that are released by DC, and both have antigen-presenting capacities. However, the physiological role of antigen presentation by EV is still unclear. We here demonstrate that the release of small EV by activated DC is strongly stimulated by phagocytic events. We show that, concomitant with the enhanced release of EV, a significant proportion of phagocytosed bacteria was expulsed back into the medium. High-resolution fluorescence microscopic images revealed that bacteria in phagosomes were surrounded by EV marker-proteins. Moreover, expulsed bacteria were often found associated with clustered HLA II and CD63. Together, these observations suggest that exosomes may be formed by the inward budding into phagosomes, whereupon they are secreted together with the phagosomal content. These findings may have important implications for selective loading of peptides derived from phagocytosed pathogens onto exosome associated HLA molecules, and have important implications for vaccine design.

摘要

树突状细胞 (DC) 具有独特的能力，可通过呈递来自与主要组织相容性复合体 (MHC) 分子结合的外源性抗原的 T 细胞受体特异性肽来激活幼稚 T 细胞。MHC 分子展示在 DC 质膜以及 DC 释放的细胞外囊泡 (EV) 上，两者都具有抗原呈递能力。然而，EV 抗原呈递的生理作用仍不清楚。我们在此证明，吞噬事件强烈刺激激活的 DC 释放小 EV。我们发现，随着 EV 释放的增强，很大一部分被吞噬的细菌被排出回培养基中。高分辨率荧光显微图像显示，吞噬体中的细菌被 EV 标记蛋白包围。此外，排出的细菌经常被发现与聚集的 HLA II 和 CD63 相关。总之，这些观察结果表明，外泌体可能是通过向内出芽形成吞噬体而形成的，随后它们与吞噬体内容物一起分泌。这些发现可能对于将来自吞噬病原体的肽选择性负载到外泌体相关的 HLA 分子上具有重要意义，并对疫苗设计具有重要意义。