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

TitleThe comings and goings of MHC class I molecules herald a new dawn in cross-presentation.
Publication TypeJournal Article
Year of Publication2016
AuthorsJ Blander, M
JournalImmunol Rev
Volume272
Issue1
Pagination65-79
Date Published2016 Jul
ISSN1600-065X
Abstract

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.

DOI10.1111/imr.12428
Alternate JournalImmunol. Rev.
PubMed ID27319343
PubMed Central IDPMC4942502
Grant ListP01 DK072201 / DK / NIDDK NIH HHS / United States
R01 AI073899 / AI / NIAID NIH HHS / United States
R01 AI095245 / AI / NIAID NIH HHS / United States
R01 AI123284 / AI / NIAID NIH HHS / United States