Intracellular recycling and cross‐presentation by MHC class I molecules. Issue 1 (20th June 2016)

• Record Type: Journal Article
• Authors: van Endert, Peter
• Is Part Of: Immunological reviews. Volume 272:Issue 1(2016)
• Page Start: 80
• Page End: 96
• Publication Date: 2016-06-20
• Subjects: MHC class I -- cross‐presentation -- endosome; Immunology -- Periodicals; Transplantation of organs, tissues, etc -- Periodicals; 616.079
• DOI: 10.1111/imr.12424
• Languages: English
• ISSNs: 0105-2896

Abstract

Summary: Cross‐presentation of internalized antigens by dendritic cells requires efficient delivery of Major Histocompatibility Complex (MHC) class I molecules to peptide‐loading compartments. Strong evidence suggests that such loading can occur outside of the endoplasmic reticulum; however, the trafficking pathways and sources of class I molecules involved are poorly understood. Examination of non‐professional, non‐phagocytic cells has revealed a clathrin‐independent, Arf6‐dependent recycling pathway likely traveled by internalized optimally loaded (closed) class I molecules. Some closed and all open MHC class I molecules travel to late endosomes to be degraded but might also partly be re‐loaded with peptides and recycled. Studies of viral interference revealed pathways in which class I molecules are directed to degradation in lysosomes upon ubiquitination at the surface, or upon AP‐1 and HIV‐nef‐dependent misrouting from the Golgi network to lysosomes. While many observations made in non‐professional cells remain to be re‐examined in dendritic cells, available evidence suggests that both recycling and neo‐synthesized class I molecules can be loaded with cross‐presented peptides. Recycling molecules can be recruited to phagosomes triggered by innate signals such as TLR4 ligands, and may therefore specialize in loading with phagocytosed antigens. In contrast, AP‐1‐dependent accumulation at, or trafficking through, a Golgi compartment of newly synthesized molecules appears to be important for cross‐presentation of soluble proteins and possibly of long peptides that are processed in the so‐called vacuolar pathway. However, significant cell biological work will be required to confirm this or any other model and to integrate knowledge on MHC class I biochemistry and trafficking in models of CD8 + T‐cell priming by dendritic cells.