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TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming
- Source :
- Nature immunology. 22(4)
- Publication Year :
- 2020
-
Abstract
- Classic major histocompatibility complex class I (MHC-I) presentation relies on shuttling cytosolic peptides into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). Viruses disable TAP to block MHC-I presentation and evade cytotoxic CD8+ T cells. Priming CD8+ T cells against these viruses is thought to rely solely on cross-presentation by uninfected TAP-functional dendritic cells. We found that protective CD8+ T cells could be mobilized during viral infection even when TAP was absent in all hematopoietic cells. TAP blockade depleted the endosomal recycling compartment of MHC-I molecules and, as such, impaired Toll-like receptor-regulated cross-presentation. Instead, MHC-I molecules accumulated in the ER-Golgi intermediate compartment (ERGIC), sequestered away from Toll-like receptor control, and coopted ER-SNARE Sec22b-mediated vesicular traffic to intersect with internalized antigen and rescue cross-presentation. Thus, when classic MHC-I presentation and endosomal recycling compartment-dependent cross-presentation are impaired in dendritic cells, cell-autonomous noncanonical cross-presentation relying on ERGIC-derived MHC-I counters TAP dysfunction to nevertheless mediate CD8+ T cell priming.
- Subjects :
- 0301 basic medicine
Male
T cell
Immunology
Priming (immunology)
Golgi Apparatus
CD8-Positive T-Lymphocytes
Major histocompatibility complex
Endoplasmic Reticulum
Lymphocyte Activation
03 medical and health sciences
0302 clinical medicine
Cross-Priming
Antigen
Orthomyxoviridae Infections
medicine
Immunology and Allergy
Cytotoxic T cell
Animals
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 2
Cells, Cultured
Cell Proliferation
Mice, Knockout
Mice, Inbred BALB C
biology
Chemistry
Histocompatibility Antigens Class I
Cross-presentation
Transporter associated with antigen processing
Dendritic Cells
Coculture Techniques
Cell biology
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Influenza A virus
Host-Pathogen Interactions
biology.protein
ATP-Binding Cassette Transporters
Female
CD8
030215 immunology
Subjects
Details
- ISSN :
- 15292916
- Volume :
- 22
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Nature immunology
- Accession number :
- edsair.doi.dedup.....5a4f3921d8115fcddc8d4aac4a83d297