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.
journal_name
Elifejournal_title
eLifeauthors
Tullett KM,Tan PS,Park HY,Schittenhelm RB,Michael N,Li R,Policheni AN,Gruber E,Huang C,Fulcher AJ,Danne JC,Czabotar PE,Wakim LM,Mintern JD,Ramm G,Radford KJ,Caminschi I,O'Keeffe M,Villadangos JA,Wright MD,Blewittdoi
10.7554/eLife.63452subject
Has Abstractpub_date
2020-12-02 00:00:00issn
2050-084Xpii
63452journal_volume
9pub_type
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