1. Distinct antigen uptake receptors route to the same storage compartments for cross-presentation in dendritic cells.
- Author
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Ho NI, Camps MG, Garcia-Vallejo JJ, Bos E, Koster AJ, Verdoes M, van Kooyk Y, and Ossendorp F
- Subjects
- Animals, Antigen Presentation, Antigens immunology, Cathepsins metabolism, Dendritic Cells metabolism, Dendritic Cells ultrastructure, Endosomes immunology, Endosomes metabolism, Endosomes ultrastructure, Histocompatibility Antigens Class I metabolism, Histocompatibility Antigens Class II metabolism, Lysosomes immunology, Lysosomes metabolism, Lysosomes ultrastructure, Mice, Microscopy, Electron, Transmission, Models, Animal, NIH 3T3 Cells, Primary Cell Culture, Antigens metabolism, Cross-Priming, Dendritic Cells immunology, Lectins, C-Type metabolism, Receptors, IgG metabolism
- Abstract
An exclusive feature of dendritic cells (DCs) is their capacity to present exogenous antigens by MHC class I molecules, called cross-presentation. Here, we show that protein antigen can be conserved in mature murine DCs for several days in a lysosome-like storage compartment, distinct from MHC class II and early endosomal compartments, as an internal source for the supply of MHC class I ligands. Using two different uptake routes via Fcγ receptors and C-type lectin receptors, we could show that antigens were routed towards the same endolysosomal compartments after 48 h. The antigen-containing compartments lacked co-expression of molecules involved in MHC class I processing and presentation including TAP and proteasome subunits as shown by single-cell imaging flow cytometry. Moreover, we observed the absence of cathepsin S but selective co-localization of active cathepsin X with protein antigen in the storage compartments. This indicates cathepsin S-independent antigen degradation and a novel but yet undefined role for cathepsin X in antigen processing and cross-presentation by DCs. In summary, our data suggest that these antigen-containing compartments in DCs can conserve protein antigens from different uptake routes and contribute to long-lasting antigen cross-presentation., (© 2021 The Authors. Immunology published by John Wiley & Sons Ltd.)
- Published
- 2021
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