PMID- 27846572
OWN - NLM
STAT- MEDLINE
DCOM- 20170407
LR  - 20220129
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Linking)
VI  - 354
IP  - 6310
DP  - 2016 Oct 21
TI  - A large fraction of HLA class I ligands are proteasome-generated spliced 
      peptides.
PG  - 354-358
AB  - 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.
CI  - Copyright (c) 2016, American Association for the Advancement of Science.
FAU - Liepe, Juliane
AU  - Liepe J
AD  - Centre for Integrative Systems Biology and Bioinformatics, Department of Life 
      Sciences, Imperial College London, London SW7 2AZ, UK. michele.mishto@charite.de 
      j.liepe@imperial.ac.uk.
FAU - Marino, Fabio
AU  - Marino F
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      3584 CH Utrecht, Netherlands.
AD  - Netherlands Proteomics Centre, CH Utrecht, Netherlands.
FAU - Sidney, John
AU  - Sidney J
AD  - Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La 
      Jolla, CA 92037, USA.
FAU - Jeko, Anita
AU  - Jeko A
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      3584 CH Utrecht, Netherlands.
AD  - Netherlands Proteomics Centre, CH Utrecht, Netherlands.
FAU - Bunting, Daniel E
AU  - Bunting DE
AD  - Centre for Integrative Systems Biology and Bioinformatics, Department of Life 
      Sciences, Imperial College London, London SW7 2AZ, UK.
FAU - Sette, Alessandro
AU  - Sette A
AD  - Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La 
      Jolla, CA 92037, USA.
FAU - Kloetzel, Peter M
AU  - Kloetzel PM
AD  - Institut fur Biochemie, Charite-Universitatsmedizin Berlin, 10117 Berlin, 
      Germany.
AD  - Berlin Institute of Health, 10117 Berlin, Germany.
FAU - Stumpf, Michael P H
AU  - Stumpf MP
AD  - Centre for Integrative Systems Biology and Bioinformatics, Department of Life 
      Sciences, Imperial College London, London SW7 2AZ, UK.
FAU - Heck, Albert J R
AU  - Heck AJ
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      3584 CH Utrecht, Netherlands.
AD  - Netherlands Proteomics Centre, CH Utrecht, Netherlands.
FAU - Mishto, Michele
AU  - Mishto M
AD  - Institut fur Biochemie, Charite-Universitatsmedizin Berlin, 10117 Berlin, 
      Germany. michele.mishto@charite.de j.liepe@imperial.ac.uk.
AD  - Berlin Institute of Health, 10117 Berlin, Germany.
LA  - eng
SI  - Dryad/10.5061/dryad.r984n
GR  - BB/G007934/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - NC/K001949/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction 
      of Animals in Research/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161020
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Ligands)
RN  - 0 (Peptides)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - *Antigen Presentation
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line, Tumor
MH  - Computational Biology
MH  - Epitopes, T-Lymphocyte/*metabolism
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Ligands
MH  - Peptides/immunology/metabolism
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Splicing
EDAT- 2016/11/16 06:00
MHDA- 2017/04/08 06:00
CRDT- 2016/11/16 06:00
PHST- 2016/02/12 00:00 [received]
PHST- 2016/09/19 00:00 [accepted]
PHST- 2016/11/16 06:00 [entrez]
PHST- 2016/11/16 06:00 [pubmed]
PHST- 2017/04/08 06:00 [medline]
AID - 354/6310/354 [pii]
AID - 10.1126/science.aaf4384 [doi]
PST - ppublish
SO  - Science. 2016 Oct 21;354(6310):354-358. doi: 10.1126/science.aaf4384. Epub 2016 
      Oct 20.