期刊
SCIENCE
卷 354, 期 6310, 页码 354-358出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaf4384
关键词
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资金
- Berlin Institute of Health [CRG1-TP1]
- Einstein Stiftung Berlin grant [A2013-174]
- NC3Rs through David Sainsbury Fellowship [NC/K001949/1]
- BBSRC [BB/G007934/1]
- HFSP [RGP0061/2011]
- Leverhulme Trust [F/07058/BP]
- Royal Society through a Wolfson Research Merit Award
- Proteins@Work [184.032.201]
- Gravity Program Institute for Chemical Immunology
- Netherlands Organisation for Scientific Research
- BBSRC [BB/G007934/1, BB/K017284/1, BB/L023776/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/L023776/1, BB/G007934/1, BB/K017284/1] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/K001949/1] Funding Source: researchfish
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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