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Antigen Uptake, Processing, and Presentation by Dendritic Cells

  • Walter Gottlieb Land
Chapter

Abstract

In this chapter, the major mechanisms of antigen uptake, processing, and presentation by antigen-presenting cells, in particular dendritic cells, are compendiously explored. In the course of these processes, immature dendritic cells mature into immunostimulatory cells able to activate CD4+ and CD8+ T cells. Initial uptake of exogenous antigens is provided by mainly three phagocytic pathways, (1) receptor-mediated endocytosis, (2) phagocytosis, and (3) macropinocytosis. Engulfed exogenous antigens are prepared for further processing and presentation. By contrast, host-derived endogenous antigens are channelled for further processing and presentation via the cell-intrinsic machinery of autophagy. Depending on exogenous or endogenous sources, distinct pathways are involved in processing and presentation of antigenic peptides loaded on MHC molecules. Exogenous antigenic proteins are processed to peptides in endolysosomal compartments to be loaded on MHC-II molecules biosynthesized in the endoplasmic reticulum. The peptide/MHC-II complexes leave the endosomal antigen-processing compartments to be transported to and inserted into the plasma membrane for T cell recognition by CD4+ T cells. However, exogenous antigenic proteins, when degraded to peptides by the immunoproteasome or processed in endocytic compartments, can also be loaded on MHC-I molecules to be cross-presented to CD8+ T cells. On the other hand, endogenous cytosolic antigenic proteins are processed to peptides in complex proteasome-dependent and proteasome-independent pathways to be loaded on MHC-I molecules in the endoplasmic reticulum. The peptide/MHC-I complexes then leave within vesicles for transport through the Golgi apparatus to become inserted into plasma membrane for T cell recognition by CD8+ T cells. However, endogenous antigenic proteins can also be loaded on MHC-II molecules via involvement of autophagic processes to be cross-presented to CD4+ T cells. Notably, a potentially crucial role of DAMPs in the scenario of both direct antigen presentation and cross-presentation is finally discussed.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of StrasbourgMolecular ImmunoRheumatology, Laboratory of Excellence TransplantexStrasbourgFrance

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