期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：48
页码：20377-20381
DOI：10.1073/pnas.0910295106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Presentation of exogenous antigens on MHC class I molecules, termed cross-presentation, is essential for the induction of CD8 T-cell responses and is carried out by specialized dendritic cell (DC) subsets. The mechanisms involved remain unclear. It has been proposed that antigens could be transported by endocytic receptors, such as the mannose receptor (MR) in the case of soluble ovalbumin, into early endosomes in which the cross-presentation machinery would be recruited. In these endosomal compartments, peptides would be trimmed by the aminopeptidase IRAP before loading onto MHC class I molecules. Here, we have investigated the contribution of this pathway to cross-presentation by steady-state CD8+ DC and inflammatory monocyte-derived DC (moDC) generated in vivo. We demonstrate that IRAP and MR are dispensable for cross-presentation by CD8+ DC and for cross-priming. Moreover, we could not find any evidence for diversion of endocytosed antigen into IRAP-containing endosomes in these cells. However, cross-presentation was impaired in moDC deficient in IRAP or MR, confirming the role of these two molecules in inflammatory DC. These results demonstrate that the mechanisms responsible for cross-priming by steady-state and inflammatory DC are different, which has important implications for vaccine design.
