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  A large fraction of HLA class I ligands are proteasome-generated spliced peptides.

Liepe, J., Marino, F., Sidney, J., Jeko, A., Bunting, D. E., Sette, A., et al. (2016). A large fraction of HLA class I ligands are proteasome-generated spliced peptides. Science, 354(6310), 354-358. doi:10.1126/science.aaf4384.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-CFBD-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-CFC6-8
Genre: Journal Article

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2472947.pdf (Publisher version), 739KB
 
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 Creators:
Liepe, J.1, Author              
Marino, F., Author
Sidney, J., Author
Jeko, A., Author
Bunting, D. E., Author
Sette, A., Author
Kloetzel, P. M., Author
Stumpf, M.l P. H., Author
Heck, A. J. R., Author
Mishto, M., Author
Affiliations:
1Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_2466694              

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 Abstract: The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8+ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular and distinguishing features. We validated this observation using a range of complementary experimental and bioinformatics approaches, as well as multiple cell types. The widespread appearance and abundance of proteasome-catalyzed peptide splicing events has implications for immunobiology and autoimmunity theories and may provide a previously untapped source of epitopes for use in vaccines and cancer immunotherapy.

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Language(s): eng - English
 Dates: 2016-10-21
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1126/science.aaf4384
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Title: Science
Source Genre: Journal
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Pages: - Volume / Issue: 354 (6310) Sequence Number: - Start / End Page: 354 - 358 Identifier: -