The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules

Abstract

To monitor the health of cells, the immune system tasks antigen presenting cells with gathering antigens from other cells and reporting them to CD8 T cells in the form of peptides bound to MHC I molecules. Most cells would be unable to perform this function because they use their MHC I molecules to exclusively present peptides derived from the cell’s own proteins. However, the immune system evolved mechanisms for dendritic cells and some other phagocytes to sample and present antigens from the extracellular milieu on MHC I through a process called cross-presentation (XPT). How this important task is accomplished, its role in health and disease and its potential for exploitation are the subject of this review.

By Capturing Inflammatory Lipids Released from Dying Cells, the Receptor CD14 Induces Inflammasome-Dependent Phagocyte Hyperactivation

“…It remains unclear how oxPAPC is delivered from endosomes into the cytosol. We note several other immunological processes involve such a transport event, such as the transport of extracellular antigens to the MHC class I machinery (Cruz et al, 2017), and the delivery of peptidoglycan fragments to NOD1 and NOD2 in the cytosol (Philpott et al, 2014). Our knowledge of how endosomal molecules are transported to the cytosol remains limited.…”

Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis

“…In addition to a large body of evidence indicating that the proteasome is the origin of most antigens presented via MHC class I molecules, some evidence indicates that other proteases can contribute to antigen processing (Cruz et al, 2017; Münz, 2016; Rock et al, 2010). Most notably, the lysosomal protease cathepsin S has been found to facilitate antigen generation in DCs in the endosomal-lysosomal compartment before being presented by MHC class I molecules (Hari et al, 2015; Shen et al, 2004).…”

“…Apart from the ability of DCs to present peptide antigens from their cytoplasm, these cells are also involved in the uptake and processing of extracellular antigens with MHC class I molecules to CD8 + T cells by cross presentation (Cruz et al, 2017). Recently, it was noted that, in addition to foreign protein, DCs can also take up complete antigen-MHC class I (and II) complexes and present them to T cells, a process termed “cross-dressing” (Nakayama, 2015).…”

Turbocharging vaccines: emerging adjuvants for dendritic cell based therapeutic cancer vaccines

“…Dendritic cells (DCs) are recognized for their unmatched capacity for activating both innate and adaptive immune pathways [1]. Moreover, DCs in general and CD141 + DCs in particular (Fig 1), are unique in their ability for processing exogenous tumor antigens through their cross-presentation pathway and facilitating activation of tumor specific CD8 + cytotoxic T lymphocytes (CTLs) [2]. As a result, new cancer vaccine strategies (BOX2) consider adjuvants that activate cross-presenting DCs to yield maximum clinical success.…”