PXD044235

PXD044235 is an original dataset announced via ProteomeXchange.

Title	A lysine residue at the C-terminus of MHC class I ligands correlates with low C-terminal proteasomal cleavage probability
Description	The majority of peptides presented by MHC class I results from proteasomal protein turnover. The specialized immunoproteasome, which is induced during inflammation, plays a major role in antigenic peptide generation. However, other cellular proteases can, either alone or together with the proteasome, contribute peptides for MHC class I loading non-canonically. We used an im-munopeptidomics workflow combined with a prediction software for proteasomal cleavage probabilities to analyze how inflammatory conditions affect proteasomal processing of immune epitopes presented by A549 cells. Treatment of A549 cells with IFNγ enhanced proteasomal cleavage probability of MHC class I ligands for both, the constitutive proteasome and the im-munoproteasome. Furthermore, IFNγ alters the contribution of the different HLA allotypes to the immunopeptidome. When we calculated HLA allotype-specific proteasomal cleavage probabili-ties for MHC class I ligands, peptides presented by HLA-A*30:01 showed characteristics hinting at a reduced C-terminal proteasomal cleavage probability independently of the type of proteasome. This was confirmed by HLA-A*30:01 ligands from the immune epitope database, which also showed this effect. Furthermore, two additional HLA allotypes, namely HLA-A*03:01 and HLA-A*11:01, presented peptides with a markedly reduced C-terminal proteasomal cleavage probability. Peptides eluted from all three HLA allotypes shared a peptide binding motif with a C-terminal lysine residue suggesting that this lysine residue impairs proteasome-dependent HLA ligand production and might, in turn, favor peptide generation by other cellular proteases. The mass spectrometry raw files used in this study were originally produced for a previous publication, where they were utilized to address the influence of cigarette smoke on the antiviral T-cell immune response. Here, we have reanalyzed the data to investigate processing of MHC class I ligands by c20S or i20S, respectively. Original publication: Chen, J.; Wang, X.; Schmalen, A.; Haines, S.; Wolff, M.; Ma, H.; Zhang, H.; Stoleriu, M.G.; Nowak, J.; Nakayama, M.; et al. Antiviral CD8(+) T cell immune responses are impaired by cigarette smoke and in COPD. Eur Respir J 2023, doi:10.1183/13993003.01374-2022.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:07:51.966.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adrian Schmalen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-31 10:57:37	ID requested
1	2023-10-24 11:35:23	announced
2	2023-11-14 09:04:37	announced	2023-11-14: Updated project metadata.
⏵ 3	2023-11-14 09:08:03	announced	2023-11-14: Updated project metadata.

Schmalen A, Kammerl IE, Meiners S, Noessner E, Deeg CA, Hauck SM, A Lysine Residue at the C-Terminus of MHC Class I Ligands Correlates with Low C-Terminal Proteasomal Cleavage Probability. Biomolecules, 13(9):(2023) [pubmed]

Chen J, Wang X, Schmalen A, Haines S, Wolff M, Ma H, Zhang H, Stoleriu MG, Nowak J, Nakayama M, Bueno M, Brands J, Mora AL, Lee JS, Krauss-Etschmann S, Dmitrieva A, Frankenberger M, Hofer TP, Noessner E, Moosmann A, Behr J, Milger K, Deeg CA, Staab-Weijnitz CA, Hauck SM, Adler H, Goldmann T, Gaede KI, Behrends J, Kammerl IE, Meiners S, T-cell immune responses are impaired by cigarette smoke and in COPD. Eur Respir J, 62(2):(2023) [pubmed]

submitter keyword: immunopeptidomics

proteasome-independent

non-canonical MHC class I ligands

HLA-A*03:01

HLA-A*11:01

HLA-A*30:01

proteasomal cleavage probability

peptide origin

peptide processing

Stefanie M. Hauck
contact affiliation	Core Facility - Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
contact email	stefanie.hauck@helmholtz-munich.de
lab head
Adrian Schmalen
contact affiliation	Chair of Physiology, Department of Veterinary Sciences, LMU Munich, Martinsried, Germany; Metabolomics and Proteomics Core, Helmholtz Center Munich, Germany
contact email	adrian.schmalen@tiph.vetmed.uni-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044235
     1. Label: PRIDE project
     2. Name: A lysine residue at the C-terminus of MHC class I ligands correlates with low C-terminal proteasomal cleavage probability