Into the Intracellular Logistics of Cross-Presentation

Jacques Neefjes,Charlotte Sadaka

doi:10.3389/fimmu.2012.00031

Abstract

The induction of cytotoxic CD8+ T cell responses requires the presentation of antigenic peptides by MHC class I molecules (MHC I). MHC I usually present peptides derived from endogenous proteins. However, some subtypes of dendritic cells have developed the ability to efficiently present peptides derived from exogenous antigens on MHC I via a process called cross-presentation. Cross-presentation is intimately linked to the induction of anti-viral, -bacterial, and -tumor cytotoxic T cell (CTL) responses, as well as a wide variety of CTL-mediated diseases and transplant rejections. The molecular and cellular mechanisms underlying cross-presentation have been studied intensively since its original description, yet understanding of this process is incomplete and on the forefront of immunological research. Numerous pathways and models, some of them conflicting, have been described so far. Here, we review the various pathways reported as involved in cross-presentation, highlighting the complexity of this process. We also discuss in detail the different intracellular steps required, from antigen capture and routing, to processing, and finally peptide loading, emphasizing the need for a better understanding of the cell biology of this phenomenon.

Highlights

The mammalian adaptive immune response is crucial in the clearance of many infections
Endocytosed antigens can be processed for cross-presentation by different pathways most likely displaying distinct proteolytic specificities: (1) by endosomal proteases such as cathepsin S and D (Fonteneau et al, 2003; Shen et al, 2004) and (2) by the cytosolic proteasomal machinery used in the classical MHC Class I (MHC I) antigen presentation pathway (Fonteneau et al, 2003; Shen et al, 2004; Neefjes et al, 2011) which implies that exogenous antigens find a way to enter the cytosol for degradation by the proteasome
The many conflicting opinions in the field might be partially explained by the fact that the process has different requirements depending on the cell type (e.g., CD8α+ vs CD8α− dendritic cells (DCs) or monocytes-derived DCs (Mo-DCs)), on the antigen form, and source, and on the uptake route

Summary

Introduction

The mammalian adaptive immune response is crucial in the clearance of many infections. For cross-presentation, exogenous antigens (e.g., from an infected cell) are taken up by DCs and rerouted to the MHC I pathway for presentation to and activation of CD8+ T cells.

Results

Conclusion