PXD032054-2

PXD032054 is an original dataset announced via ProteomeXchange.

Title	Mutations in epitope flanking regions for SARS-CoV-2 nucleoprotein affect proteasomal processing to alter CD8+ T cell responses
Description	Viral CD8+ epitopes are generated by the cellular turnover of viral proteins, predominantly by the proteasome1. Mutations located within viral epitopes can result in escape from memory T cells2. Focussing on two of the most dominant SARS-CoV-2 nucleoprotein CD8+ epitopes3,4, we identified mutations in epitope flanking regions. Using SARS-CoV-2 nucleoprotein transduced B cell lines and in vitro proteasomal processing of peptides, we investigated the contribution of these mutations to antigen processing and T cell activation. We found that decreased NP9-17-B*27:05 CD8+ T cell responses to the NP-Q7K mutation correlated with lower epitope surface expression, likely due to a lack of efficient epitope production by the proteasome and suggesting an immune escape caused by this mutation. In contrast, NP-P6L and NP-D103N/Y mutations flanking the NP9-17-B*27:05 and NP105-113-B*07:02 epitopes, respectively, increased CD8+ T cell responses associated with enhanced epitope production by the proteasome. Our results provide evidence that SARS-CoV-2 mutations outside the epitope could have significant impact on antigen processing and presentation, thereby contributing to escape from immunodominant T cell responses. Alternatively, mutations could enhance antigen processing and T cell efficacy, opening new avenues for improving future vaccine designs.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:08:35.043.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhanru Yu
SpeciesList	scientific name: recombinant SARS coronavirus; NCBI TaxID: 575560;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-03 12:51:53	ID requested
1	2023-10-24 12:01:23	announced
⏵ 2	2023-11-14 09:08:37	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:09:25	announced	2024-10-22: Updated project metadata.

Wellington D, Yin Z, Yu Z, Heilig R, Davis S, Fischer R, Felce SL, Antoun E, Hublitz P, Beveridge R, Dong D, Liu G, Yao X, Peng Y, Kessler BM, Dong T, T cell responses. Heliyon, 9(10):e20076(2023) [pubmed]

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: LC-MS/MS, SARS-CoV-2, T-cell, Antigen, Epitope

Roman Fischer
contact affiliation	Discovery Proteomics Facility, Target Discovery Institute,University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Zhanru Yu
contact affiliation	TDI, University of Oxford
contact email	zhanru.yu@ndm.ox.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD032054

PRIDE project URI

• PRIDE
  1. PXD032054
     1. Label: PRIDE project
     2. Name: Mutations in epitope flanking regions for SARS-CoV-2 nucleoprotein affect proteasomal processing to alter CD8+ T cell responses