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RNF41 regulates the damage recognition receptor Clec9A and antigen cross-presentation in mouse dendritic cells
- Source :
- eLife, eLife, Vol 9 (2020)
- Publication Year :
- 2020
- Publisher :
- eLife Sciences Publications, Ltd, 2020.
-
Abstract
- The dendritic cell receptor Clec9A facilitates processing of dead cell-derived antigens for cross-presentation and the induction of effective CD8+ T cell immune responses. Here, we show that this process is regulated by E3 ubiquitin ligase RNF41 and define a new ubiquitin-mediated mechanism for regulation of Clec9A, reflecting the unique properties of Clec9A as a receptor specialized for delivery of antigens for cross-presentation. We reveal RNF41 is a negative regulator of Clec9A and the cross-presentation of dead cell-derived antigens by mouse dendritic cells. Intriguingly, RNF41 regulates the downstream fate of Clec9A by directly binding and ubiquitinating the extracellular domains of Clec9A. At steady-state, RNF41 ubiquitination of Clec9A facilitates interactions with ER-associated proteins and degradation machinery to control Clec9A levels. However, Clec9A interactions are altered following dead cell uptake to favor antigen presentation. These findings provide important insights into antigen cross-presentation and have implications for development of approaches to modulate immune responses.
- Subjects :
- 0301 basic medicine
CD4-Positive T-Lymphocytes
Mouse
CD8-Positive T-Lymphocytes
Mice
0302 clinical medicine
Immunology and Inflammation
Cricetinae
Biology (General)
Receptors, Immunologic
Mice, Knockout
biology
Chemistry
General Neuroscience
DAMP recognition
Cross-presentation
General Medicine
Cell biology
Ubiquitin ligase
medicine.anatomical_structure
E3 ubiquitin ligase
Medicine
Research Article
Protein Binding
QH301-705.5
T cell
Science
Ubiquitin-Protein Ligases
Antigen presentation
CHO Cells
ubiquitination
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Immune system
Cricetulus
Antigen
medicine
Animals
Lectins, C-Type
Antigens
General Immunology and Microbiology
Dendritic cell
Dendritic Cells
Mice, Inbred C57BL
antigen presentation
030104 developmental biology
Gene Expression Regulation
biology.protein
030217 neurology & neurosurgery
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....7dad18f93efe94b8043c45cc1ae04472