Peptidases released by necrotic cells control CD8+ T cell cross-priming.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Manns, Michael P
White, Ayla O
Citrin, Deborah E
Greten, Tim F
MetadataShow full item record
AbstractCross-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.
CitationPeptidases released by necrotic cells control CD8+ T cell cross-priming. 2013: J. Clin. Invest.
The following license files are associated with this item:
- Mechanism of dichotomy between CD8+ responses elicited by apoptotic and necrotic cells.
- Authors: Buckwalter MR, Srivastava PK
- Issue date: 2013
- A marked reduction in priming of cytotoxic CD8+ T cells mediated by stress-induced glucocorticoids involves multiple deficiencies in cross-presentation by dendritic cells.
- Authors: Hunzeker JT, Elftman MD, Mellinger JC, Princiotta MF, Bonneau RH, Truckenmiller ME, Norbury CC
- Issue date: 2011 Jan 1
- Adenovirus Vector Harboring the HBcAg and Tripeptidyl Peptidase II Genes Induces Potent Cellular Immune Responses In Vivo.
- Authors: Tan Q, Ma S, Hu J, Chen X, Yu Y, Tang Z, Zang G
- Issue date: 2017
- Calpains Released from Necrotic Tumor Cells Enhance Antigen Cross-Presentation to Activate CD8<sup>+</sup> T Cells In Vitro.
- Authors: Shields NJ, Peyroux EM, Campbell K, Mehta S, Woolley AG, Counoupas C, Neumann S, Young SL
- Issue date: 2022 Sep 14
- The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice.
- Authors: Zelenay S, Keller AM, Whitney PG, Schraml BU, Deddouche S, Rogers NC, Schulz O, Sancho D, Reis e Sousa C
- Issue date: 2012 May