Distinct antigen uptake receptors route to the same storage compartments for cross-presentation in dendritic cells

Nataschja I. Ho, Marcel G. Camps, Juan J. Garcia-Vallejo, Erik Bos, Abraham J. Koster, Martijn Verdoes, Yvette van Kooyk, Ferry Ossendorp*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)494-506
Number of pages13
Issue number3
Publication statusPublished - 1 Nov 2021

Cite this