The comings and goings of MHC class I molecules herald a new dawn in cross-presentation

• Published in: Immunological reviews 2016-07, Vol.272 (1), p.65-79
• Main Author: Blander, J. Magarian
• Format: Article
• Language: English
• Subjects: Animals; antigen presentation/processing; Antigen processing; Antigens; ATP-Binding Cassette Sub-Family B Member 2 - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cross-Priming; Dendritic cells; Dendritic Cells - immunology; Endocytosis; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Golgi apparatus; Histocompatibility Antigens Class I - metabolism; Humans; Immune Tolerance; Immunological tolerance; infection; Infection - immunology; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Microorganisms; Molecular chains; Peptides; phagocytosis; Phagosomes; Phagosomes - metabolism; Proteasome Endopeptidase Complex - metabolism; Proteasomes; Receptors; Relaying; Toll-like receptors/pattern recognition receptors
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12428

Summary MHC class I (MHC‐I) molecules are the centerpieces of cross‐presentation. They are loaded with peptides derived from exogenous sources and displayed on the plasma membrane to communicate with CD8 T cells, relaying a message of tolerance or attack. The study of cross‐presentation has been focused on the relative contributions of the vacuolar versus cytosolic pathways of antigen processing and the location where MHC‐I molecules are loaded. While vacuolar processing generates peptides loaded onto vacuolar MHC‐I molecules, how and where exogenous peptides generated by the proteasome and transported by TAP meet MHC‐I molecules for loading has been a matter of debate. The source and trafficking of MHC‐I molecules in dendritic cells have largely been ignored under the expectation that these molecules came from the Endoplasmic reticulum (ER) or the plasma membrane. New studies reveal a concentrated pool of MHC‐I molecules in the endocytic recycling compartment (ERC). These pools are rapidly mobilized to phagosomes carrying microbial antigens, and in a signal‐dependent manner under the control of Toll‐like receptors. The phagosome becomes a dynamic hub receiving traffic from multiple sources, the ER–Golgi intermediate compartment for delivering the peptide‐loading machinery and the ERC for deploying MHC‐I molecules that alert CD8 T cells of infection.