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

MPG-Autoren
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Liepe,  J.
Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society;

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Zitation

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.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002D-CFBD-D
Zusammenfassung
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.