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  Multi-level strategy for identifying proteasome-catalyzed spliced epitopes targeted by CD8+ T cells during bacterial infection.

Platteel, A. C. M., Liepe, J., Textoris-Taube, K., Keller, C., Henklein, P., Schalkwijk, H. H., et al. (2017). Multi-level strategy for identifying proteasome-catalyzed spliced epitopes targeted by CD8+ T cells during bacterial infection. Cell Reports, 20(5), 1242-1253. doi:10.1016/j.celrep.2017.07.026.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-0E7D-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-11B8-4
Genre: Journal Article

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 Creators:
Platteel, A. C. M., Author
Liepe, J.1, Author              
Textoris-Taube, K., Author
Keller, C., Author
Henklein, P., Author
Schalkwijk, H. H., Author
Cardoso, R., Author
Kloetzel, P. M., Author
Mishto, M., Author
Sijts, A. J. A. M., Author
Affiliations:
1Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_2466694              

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Free keywords: proteasome, peptide splicing, Listeria monocytogenes, antigen presentation, intracelllular bacteria, in silico analysis
 Abstract: Proteasome-catalyzed peptide splicing (PCPS) generates peptides that are presented by MHC class I molecules, but because their identification is challenging, the immunological relevance of spliced peptides remains unclear. Here, we developed a reverse immunology-based multi-level approach to identify proteasome-generated spliced epitopes. Applying this strategy to a murine Listeria monocytogenes infection model, we identified two spliced epitopes within the secreted bacterial phospholipase PlcB that primed antigen-specific CD8+ T cells in L. monocytogenes-infected mice. While reacting to the spliced epitopes, these CD8+ T cells failed to recognize the non-spliced peptide parts in the context of their natural flanking sequences. Thus, we here show that PCPS expands the CD8+ T cell response against L. monocytogenes by exposing spliced epitopes on the cell surface. Moreover, our multi-level strategy opens up opportunities to systematically investigate proteins for spliced epitope candidates and thus strategies for immunotherapies or vaccine design.

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Language(s): eng - English
 Dates: 2017-08-01
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.celrep.2017.07.026
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Title: Cell Reports
Source Genre: Journal
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Pages: - Volume / Issue: 20 (5) Sequence Number: - Start / End Page: 1242 - 1253 Identifier: -