Regulation of the Cell Biology of Antigen Cross-Presentation

Annual Review of Immunology
J Magarian Blander

Abstract

Antigen cross-presentation is an adaptation of the cellular process of loading MHC-I molecules with endogenous peptides during their biosynthesis within the endoplasmic reticulum. Cross-presented peptides derive from internalized proteins, microbial pathogens, and transformed or dying cells. The physical separation of internalized cargo from the endoplasmic reticulum, where the machinery for assembling peptide-MHC-I complexes resides, poses a challenge. To solve this problem, deliberate rewiring of organelle communication within cells is necessary to prepare for cross-presentation, and different endocytic receptors and vesicular traffic patterns customize the emergent cross-presentation compartment to the nature of the peptide source. Three distinct pathways of vesicular traffic converge to form the ideal cross-presentation compartment, each regulated differently to supply a unique component that enables cross-presentation of a diverse repertoire of peptides. Delivery of centerpiece MHC-I molecules is the critical step regulated by microbe-sensitive Toll-like receptors. Defining the subcellular sources of MHC-I and identifying sites of peptide loading during cross-presentation remain key challenges.

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Citations

Dec 19, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wenbin MaBenoît J Van den Eynde
Oct 4, 2019·Journal of Virology·Cosmo Z BuffaloXuefeng Ren
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Datasets Mentioned

BETA
GM-CSF
GM-130

Methods Mentioned

BETA
GTPase
super-resolution microscopy
confocal microscopy
GTPases
flow cytometry
ubiquitination
peptide exchange

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