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  CD8(+) T cells of Listeria monocytogenes-infected mice recognize both linear and spliced proteasome products.

Platteel, A. C. M., Mishto, M., Textoris-Taube, K., Keller, C., Liepe, J., Busch, D. H., et al. (2016). CD8(+) T cells of Listeria monocytogenes-infected mice recognize both linear and spliced proteasome products. European Journal of Immunology, 46(5), 1109-1118. doi:10.1002/eji.201545989.

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 Creators:
Platteel, A. C. M., Author
Mishto, M., Author
Textoris-Taube, K., Author
Keller, C., Author
Liepe, J.1, Author           
Busch, D. H., Author
Kloetzel, P. 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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 Abstract: CD8+ T cells responding to infection recognize pathogen-derived epitopes presented by MHC class-I molecules. While most of such epitopes are generated by proteasome-mediated antigen cleavage, analysis of tumor antigen processing has revealed that epitopes may also derive from proteasome-catalyzed peptide splicing (PCPS). To determine whether PCPS contributes to epitope processing during infection, we analyzed the fragments produced by purified proteasomes from a Listeria monocytogenes polypeptide. Mass spectrometry identified a known H-2Kb-presented linear epitope (LLO296-304) in the digests, as well as four spliced peptides that were trimmed by ERAP into peptides with in silico predicted H-2Kb binding affinity. These spliced peptides, which displayed sequence similarity with LLO296-304, bound to H-2Kb molecules in cellular assays and one of the peptides was recognized by CD8+ T cells of infected mice. This spliced epitope differed by one amino acid from LLO296-304 and double staining with LLO296-304- and spliced peptide-folded MHC multimers showed that LLO296-304 and its spliced variant were recognized by the same CD8+ T cells. Thus, PCPS multiplies the variety of peptides that is processed from an antigen and leads to the production of epitope variants that can be recognized by cross-reacting pathogen-specific CD8+ T cells. Such mechanism may reduce the chances for pathogen immune evasion.

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Language(s): eng - English
 Dates: 2016-03-162016-05
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1002/eji.201545989
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Title: European Journal of Immunology
Source Genre: Journal
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Pages: - Volume / Issue: 46 (5) Sequence Number: - Start / End Page: 1109 - 1118 Identifier: -