TY - JOUR
T1 - Exosome-driven transfer of tumor-associated Pioneer Translation Products (TA-PTPs) for the MHC class I cross-presentation pathway
AU - Duvallet, Emilie
AU - Boulpicante, Mathilde
AU - Yamazaki, Takahiro
AU - Daskalogianni, Chrysoula
AU - Prado Martins, Rodrigo
AU - Baconnais, Sonia
AU - Manoury, Bénédicte
AU - Fahraeus, Robin
AU - Apcher, Sébastien
N1 - Publisher Copyright:
© 2016 The Author(s). Published with license by Taylor & Francis Group, LLC © Emilie Duvallet, Mathilde Boulpicante, Takahiro Yamazaki, Chrysoula Daskalogianni, Rodrigo Prado Martins, Sonia Baconnais, Bénédicte Manoury, Robin Fahraeus, and Sébastien Apcher.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Cellular immune reactions against non-self-epitopes require activation of cytotoxic CD8+ T-cells via cross-presentation of MHC class I-restricted peptides by professional antigen presenting cells (pAPCs), with the consequent detection and elimination of cells expressing the same antigens via the endogenous (direct) pathway. The source of peptides for the endogenous pathway is constituted of alternative mRNA translation products; however, it is still unclear which source of peptides is used for cross-presentation. Furthermore, the presentation of non-canonical translation products, produced during a non-conventional translation event, on class I molecules of tumor cells has been reported but how these peptides are generated, presented to pAPCs, and their capacity to stimulate CD8+ T cells is still not known. Here, we report that pioneer translation peptides (PTPs) derived from intron or exon pre-mRNAs can serve as tumor-associated antigens (TA-PTPs) and are delivered from the producing tumor cells to pAPCs via exosomes where they are processed by the cytosolic pathway. Injection of TA-PTPs and tumor-derived exosomes efficiently induce CD8+ T-cell proliferation and prevent tumor growth in mice. Our results show that TA-PTPs represent an efficient source of antigenic peptides for CD8+ T cell activation and that full-length proteins are not required for cross-presentation. These findings can have interesting implications for generating tolerance and for designing vectors to generate vaccines.
AB - Cellular immune reactions against non-self-epitopes require activation of cytotoxic CD8+ T-cells via cross-presentation of MHC class I-restricted peptides by professional antigen presenting cells (pAPCs), with the consequent detection and elimination of cells expressing the same antigens via the endogenous (direct) pathway. The source of peptides for the endogenous pathway is constituted of alternative mRNA translation products; however, it is still unclear which source of peptides is used for cross-presentation. Furthermore, the presentation of non-canonical translation products, produced during a non-conventional translation event, on class I molecules of tumor cells has been reported but how these peptides are generated, presented to pAPCs, and their capacity to stimulate CD8+ T cells is still not known. Here, we report that pioneer translation peptides (PTPs) derived from intron or exon pre-mRNAs can serve as tumor-associated antigens (TA-PTPs) and are delivered from the producing tumor cells to pAPCs via exosomes where they are processed by the cytosolic pathway. Injection of TA-PTPs and tumor-derived exosomes efficiently induce CD8+ T-cell proliferation and prevent tumor growth in mice. Our results show that TA-PTPs represent an efficient source of antigenic peptides for CD8+ T cell activation and that full-length proteins are not required for cross-presentation. These findings can have interesting implications for generating tolerance and for designing vectors to generate vaccines.
KW - Exosomes
KW - MHC-I antigen cross presentation
KW - pioneer translation products
KW - tumor rejection
KW - vaccines
UR - http://www.scopus.com/inward/record.url?scp=84988328602&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2016.1198865
DO - 10.1080/2162402X.2016.1198865
M3 - Article
AN - SCOPUS:84988328602
SN - 2162-4011
VL - 5
JO - OncoImmunology
JF - OncoImmunology
IS - 9
M1 - e1198865
ER -