PMID- 38480730
OWN - NLM
STAT- MEDLINE
DCOM- 20240315
LR  - 20240317
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 15
IP  - 1
DP  - 2024 Mar 13
TI  - Thunder-DDA-PASEF enables high-coverage immunopeptidomics and is boosted by 
      MS(2)Rescore with MS(2)PIP timsTOF fragmentation prediction model.
PG  - 2288
LID - 10.1038/s41467-024-46380-y [doi]
LID - 2288
AB  - Human leukocyte antigen (HLA) class I peptide ligands (HLAIps) are key targets 
      for developing vaccines and immunotherapies against infectious pathogens or 
      cancer cells. Identifying HLAIps is challenging due to their high diversity, low 
      abundance, and patient individuality. Here, we develop a highly sensitive method 
      for identifying HLAIps using liquid chromatography-ion mobility-tandem mass 
      spectrometry (LC-IMS-MS/MS). In addition, we train a timsTOF-specific peak 
      intensity MS(2)PIP model for tryptic and non-tryptic peptides and implement it in 
      MS(2)Rescore (v3) together with the CCS predictor from ionmob. The optimized 
      method, Thunder-DDA-PASEF, semi-selectively fragments singly and multiply charged 
      HLAIps based on their IMS and m/z. Moreover, the method employs the high 
      sensitivity mode and extended IMS resolution with fewer MS/MS frames (300 ms TIMS 
      ramp, 3 MS/MS frames), doubling the coverage of immunopeptidomics analyses, 
      compared to the proteomics-tailored DDA-PASEF (100 ms TIMS ramp, 10 MS/MS 
      frames). Additionally, rescoring boosts the HLAIps identification by 41.7% to 
      33%, resulting in 5738 HLAIps from as little as one million JY cell equivalents, 
      and 14,516 HLAIps from 20 million. This enables in-depth profiling of HLAIps from 
      diverse human cell lines and human plasma. Finally, profiling JY and Raji cells 
      transfected to express the SARS-CoV-2 spike protein results in 16 spike HLAIps, 
      thirteen of which have been reported to elicit immune responses in human 
      patients.
CI  - (c) 2024. The Author(s).
FAU - Gomez-Zepeda, David
AU  - Gomez-Zepeda D
AUID- ORCID: 0000-0002-9467-1213
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany. david.gomez-zepeda@dkfz-heidelberg.de.
AD  - Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz) - A 
      Helmholtz Institute of the DKFZ, Mainz, Germany. 
      david.gomez-zepeda@dkfz-heidelberg.de.
AD  - German Cancer Research Center (DKFZ) Heidelberg, Division 191, Heidelberg, 
      Germany. david.gomez-zepeda@dkfz-heidelberg.de.
FAU - Arnold-Schild, Danielle
AU  - Arnold-Schild D
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany.
FAU - Beyrle, Julian
AU  - Beyrle J
AUID- ORCID: 0000-0002-5875-6260
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany.
AD  - Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz) - A 
      Helmholtz Institute of the DKFZ, Mainz, Germany.
AD  - German Cancer Research Center (DKFZ) Heidelberg, Division 191, Heidelberg, 
      Germany.
FAU - Declercq, Arthur
AU  - Declercq A
AD  - VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
AD  - Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
FAU - Gabriels, Ralf
AU  - Gabriels R
AUID- ORCID: 0000-0002-1679-1711
AD  - VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
AD  - Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
FAU - Kumm, Elena
AU  - Kumm E
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany.
FAU - Preikschat, Annica
AU  - Preikschat A
AUID- ORCID: 0000-0002-1172-6195
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany.
FAU - Lacki, Mateusz Krzysztof
AU  - Lacki MK
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany.
FAU - Hirschler, Aurelie
AU  - Hirschler A
AUID- ORCID: 0000-0001-5066-6263
AD  - BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC UMR 7178, University of 
      Strasbourg, CNRS, ProFI - FR2048, Strasbourg, France.
FAU - Rijal, Jeewan Babu
AU  - Rijal JB
AUID- ORCID: 0009-0009-6839-9947
AD  - BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC UMR 7178, University of 
      Strasbourg, CNRS, ProFI - FR2048, Strasbourg, France.
FAU - Carapito, Christine
AU  - Carapito C
AUID- ORCID: 0000-0002-0079-319X
AD  - BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC UMR 7178, University of 
      Strasbourg, CNRS, ProFI - FR2048, Strasbourg, France.
FAU - Martens, Lennart
AU  - Martens L
AUID- ORCID: 0000-0003-4277-658X
AD  - VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
AD  - Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
FAU - Distler, Ute
AU  - Distler U
AUID- ORCID: 0000-0002-8031-6384
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany.
AD  - Research Center for Immunotherapy (FZI), University Medical Center of the 
      Johannes-Gutenberg University, Mainz, Germany.
FAU - Schild, Hansjorg
AU  - Schild H
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany.
AD  - Research Center for Immunotherapy (FZI), University Medical Center of the 
      Johannes-Gutenberg University, Mainz, Germany.
FAU - Tenzer, Stefan
AU  - Tenzer S
AUID- ORCID: 0000-0003-3034-0017
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University, Mainz, Germany. tenzer@uni-mainz.de.
AD  - Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz) - A 
      Helmholtz Institute of the DKFZ, Mainz, Germany. tenzer@uni-mainz.de.
AD  - German Cancer Research Center (DKFZ) Heidelberg, Division 191, Heidelberg, 
      Germany. tenzer@uni-mainz.de.
AD  - Research Center for Immunotherapy (FZI), University Medical Center of the 
      Johannes-Gutenberg University, Mainz, Germany. tenzer@uni-mainz.de.
LA  - eng
PT  - Journal Article
DEP - 20240313
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 0 (Peptides)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Humans
MH  - *Tandem Mass Spectrometry/methods
MH  - *Peptides/chemistry
MH  - Spike Glycoprotein, Coronavirus
MH  - Chromatography, Liquid
MH  - Histocompatibility Antigens Class I/genetics
PMC - PMC10937930
COIS- The authors declare no competing interests.
EDAT- 2024/03/14 06:47
MHDA- 2024/03/15 06:43
PMCR- 2024/03/13
CRDT- 2024/03/14 00:57
PHST- 2023/02/24 00:00 [received]
PHST- 2024/02/26 00:00 [accepted]
PHST- 2024/03/15 06:43 [medline]
PHST- 2024/03/14 06:47 [pubmed]
PHST- 2024/03/14 00:57 [entrez]
PHST- 2024/03/13 00:00 [pmc-release]
AID - 10.1038/s41467-024-46380-y [pii]
AID - 46380 [pii]
AID - 10.1038/s41467-024-46380-y [doi]
PST - epublish
SO  - Nat Commun. 2024 Mar 13;15(1):2288. doi: 10.1038/s41467-024-46380-y.