Journal
ANNUAL REVIEW OF IMMUNOLOGY, VOL 36
Volume 36, Issue -, Pages 717-753Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-immunol-041015-055523
Keywords
cross-presentation; dendritic cells; endocytosis; phagocytosis; MHC class I; Toll-like receptors
Categories
Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI073899, R01AI127658, R01AI123284, R56AI073899] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK111862, P01DK072201] Funding Source: NIH RePORTER
- NIAID NIH HHS [R56 AI073899, R01 AI123284, R01 AI127658, R01 AI073899] Funding Source: Medline
- NIDDK NIH HHS [P01 DK072201, R01 DK111862] Funding Source: Medline
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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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