RNF41 regulates the damage recognition receptor Clec9A and antigen cross-presentation in mouse dendritic cells
Journal Title
Elife
Publication Type
Journal Article
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.
Publisher
eLife Sciences
Keywords
*DAMP recognition; *E3 ubiquitin ligase; *antigen presentation; *dendritic cells; *immunology; *inflammation; *mouse; *ubiquitination
WEHI Research Division(s)
Structural Biology; Epigenetics And Development; Immunology; Blood Cells And Blood Cancer
PubMed ID
33264090
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-02-01 12:08:37
Last Modified: 2021-03-03 09:12:47
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