Antigen cross-presentation by macrophages

Abstract

This review focuses on mechanisms of antigen cross-presentation and features of this process in macrophages. Features of the crosspresentation in dendritic cells and in various macrophage phenotypes are compared. The cross-presentation can be the result of either the proteasomal or vacuolar pathway. The proteasomal pathway includes the following stages: 1) antigen capture into the phagosome; 2) antigen preservation in the phagosome; 3) antigen transfer to the cytosol and its cleavage in the proteasome to oligopeptides; 4) oligopeptide transfer into major histocompatibility complex (MHC) I-containing compartments; 5) oligopeptide loading onto the MHC I and transferring it to the cell surface. The vacuolar pathway begins in a similar way as the proteasomal pathway but differs in that the captured antigen does not leave the phagosome, but is cleaved there and loaded onto MHC I. Macrophages can use any of these pathways. Macrophages originating from blood monocytes use the vacuolar pathway; macrophages of the red pulp of the spleen use the proteasomal pathway, and peritoneal macrophages use both. The effectiveness of cross-presentation of macrophages depends on the macrophage tissue type. When developing macrophage-based methods of immunotherapy, it is important to understand the stages of both cross-presentation pathways since each of them can be considered as a target for increasing the efficiency of antigen cross-presentation and, accordingly, the effectiveness of cancer immunotherapy.