Current Concepts of Antigen Cross-Presentation

Abstract

Dendritic cells have the ability to efficiently present internalized antigens on major histocompatibility complex (MHC) I molecules. This process is termed cross-presentation and is important role in the generation of an immune response against viruses and tumors, after vaccinations or in the induction of immune tolerance. The molecular mechanisms enabling cross-presentation have been topic of intense debate since many years. However, a clear view on these mechanisms remains difficult, partially due to important remaining questions, controversial results and discussions. Here, we give an overview of the current concepts of antigen cross-presentation and focus on a description of the major cross-presentation pathways, the role of retarded antigen degradation for efficient cross-presentation, the dislocation of antigens from endosomal compartment into the cytosol, the reverse transport of proteasome-derived peptides for loading on MHC I and the translocation of the cross-presentation machinery from the ER to endosomes. We try to highlight recent advances, discuss some of the controversial data and point out some of the major open questions in the field.

Keywords: antigen dislocation; antigen processing; cross-presentation; dendritic cells; endosomes.

Figure 1

Schematic overview of cross-presentation pathways. Internalized antigens can be presented via the vacuolar pathway or via the endosome-to-cytosol pathway. In the vacuolar pathway, antigens are degraded in endosomes by Cathepsin S and loaded onto major histocompatibility complex (MHC) I there. In the endosome-to-cytosol pathway, antigens are transported into the cytosol for proteasomal degradation. Afterward, antigen-derived peptides are transported back into the endosomes (soluble and particular antigens) or into the ER (particular antigens) via TAP. There, they are trimmed by IRAP (endosomes) or ERAP (ER) and loaded onto MHC I. They cross-presentation machinery might be translocated toward endosomes via Sec22b.