Title | The comings and goings of MHC class I molecules herald a new dawn in cross-presentation. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | J Blander, M |
Journal | Immunol Rev |
Volume | 272 |
Issue | 1 |
Pagination | 65-79 |
Date Published | 2016 Jul |
ISSN | 1600-065X |
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. |
DOI | 10.1111/imr.12428 |
Alternate Journal | Immunol. Rev. |
PubMed ID | 27319343 |
PubMed Central ID | PMC4942502 |
Grant List | P01 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 |