Loading...
Peptidases released by necrotic cells control CD8+ T cell cross-priming.
Gamrekelashvili, Jaba Kapanadze, Tamar Han, Miaojun Wissing, Josef Ma, Chi Jaensch, Lothar Manns, Michael P Armstrong, Todd Jaffee, Elizabeth White, Ayla O
Gamrekelashvili, Jaba
Kapanadze, Tamar
Han, Miaojun
Wissing, Josef
Ma, Chi
Jaensch, Lothar
Manns, Michael P
Armstrong, Todd
Jaffee, Elizabeth
White, Ayla O
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2013-10-08
Submitted date
Files
Loading...
allowed publisher's PDF
Adobe PDF, 1.46 MB
Other Titles
Abstract
Cross-priming of CD8+ T cells and generation of effector immune responses is pivotal for tumor immunity as well as for successful anticancer vaccination and therapy. Dead and dying cells produce signals that can influence Ag processing and presentation; however, there is conflicting evidence regarding the immunogenicity of necrotic cell death. We used a mouse model of sterile necrosis, in which mice were injected with sterile primary necrotic cells, to investigate a role of these cells in priming of CD8+ T cells. We discovered a molecular mechanism operating in Ag donor cells that regulates cross-priming of CD8+ T cells during primary sterile necrosis and thereby controls adaptive immune responses. We found that the cellular peptidases dipeptidyl peptidase 3 (DPP-3) and thimet oligopeptidase 1 (TOP-1), both of which are present in nonimmunogenic necrotic cells, eliminated proteasomal degradation products and blocked Ag cross-presentation. While sterile necrotic tumor cells failed to induce CD8+ T cell responses, their nonimmunogenicity could be reversed in vitro and in vivo by inactivation of DPP-3 and TOP-1. These results indicate that control of cross-priming and thereby immunogenicity of primary sterile necrosis relies on proteasome-dependent oligopeptide generation and functional status of peptidases in Ag donor cells.
Citation
Peptidases released by necrotic cells control CD8+ T cell cross-priming. 2013: J. Clin. Invest.
Affiliation
Publisher
DOI
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
Description
Series/Report no.
ISSN
1558-8238
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Archived with thanks to The Journal of clinical investigation