The comings and goings of MHC class I molecules herald a new dawn in cross-presentation.
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.
Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Magarian
JM
Blander
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2 / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007239:Infections / Q000276:immunology*; D008213:Lymphocyte Activation; D010588:Phagosomes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D015395:Histocompatibility Antigens Class I; D046988:Proteasome Endopeptidase Complex
Toll-like receptors/pattern recognition receptors; antigen presentation/processing; dendritic cells; infection; major histocompatibility complex; phagocytosis