Polyglutamine-related aggregates can serve as a potent antigen source for cross-presentation by dendritic cells

Shira Tabachnick-Cherny, Sivan Pinto, Dikla Berko, Caterina Curato, Yochai Wolf, Ziv Porat, Rotem Karmona, Boaz Tirosh, Steffen Jung, Ami Navon

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Protective MHC class I dependent immune responses require an overlap between repertoires of proteins directly presented on target cells and cross-presented by professional APC, specifically dendritic cells. How stable proteins that rely on defective ribosomal proteins for direct presentation are captured for cell-To-cell transfer remains enigmatic. In this study, we address this issue using a combination of in vitro (C57BL/6-derived mouse cell lines) and in vivo (C57BL/6 mouse strains) approaches involving stable and unstable versions of OVA model Ags displaying defective ribosomal protein dependent and independent Ag presentation, respectively. Apoptosis, but not necrosis, of donor cells was found associated with robust global protein aggregate formation and captured stable proteins permissive for cross-presentation. Potency of aggregates to serve as Ag source was directly demonstrated using polyglutamine-equipped model substrates. Collectively, our data implicate global protein aggregation in apoptotic cells as a mechanism that ensures the overlap between MHC class I epitopes presented directly or cross-presented by APC and demonstrate the unusual ability of dendritic cells to process stable protein aggregates.

Original languageAmerican English
Pages (from-to)2583-2594
Number of pages12
JournalJournal of Immunology
Issue number10
StatePublished - 15 Nov 2020

Bibliographical note

Funding Information:
This work was supported by the European Research Council (AdvERC 340345 to the Jung laboratory) and the Israeli Science Foundation (887/11 to the Jung laboratory and 2038/17 to the Navon laboratory).

Publisher Copyright:
© 2020 American Association of Immunologists. All rights reserved.


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