Guermonprez Pierre, Saveanu Loredana, Kleijmeer Monique, Davoust Jean, Van Endert Peter, Amigorena Sebastian
INSERM U520, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
Nature. 2003 Sep 25;425(6956):397-402. doi: 10.1038/nature01911.
Induction of cytotoxic T-cell immunity requires the phagocytosis of pathogens, virus-infected or dead tumour cells by dendritic cells. Peptides derived from phagocytosed antigens are then presented to CD8+ T lymphocytes on major histocompatibility complex (MHC) class I molecules, a process called "cross-presentation". After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex "loading machinery" (which includes tapasin, calreticulin and Erp57). Here we show that soon after or during formation, phagosomes fuse with the ER. After antigen export to the cytosol and degradation by the proteasome, peptides are translocated by TAP into the lumen of the same phagosomes, before loading on phagosomal MHC class I molecules. Therefore, cross-presentation in dendritic cells occurs in a specialized, self-sufficient, ER-phagosome mix compartment.
细胞毒性T细胞免疫的诱导需要树突状细胞吞噬病原体、病毒感染的细胞或死亡的肿瘤细胞。然后，从吞噬的抗原衍生而来的肽在主要组织相容性复合体（MHC）I类分子上呈递给CD8 + T淋巴细胞，这一过程称为“交叉呈递”。吞噬作用后，抗原被输出到细胞质中并被蛋白酶体降解。产生的肽被认为通过与抗原呈递相关的特异性转运蛋白（TAP）转运到内质网（ER）腔中，并通过一个复杂的“装载机制”（包括塔帕辛、钙网蛋白和Erp57）装载到MHC I类分子上。在这里，我们表明吞噬体在形成后不久或形成过程中与内质网融合。在抗原输出到细胞质并被蛋白酶体降解后，肽通过TAP转运到同一吞噬体的腔内，然后再装载到吞噬体MHC I类分子上。因此，树突状细胞中的交叉呈递发生在一个特殊的、自给自足的内质网-吞噬体混合区室中。
