PXD009754

PXD009754 is an original dataset announced via ProteomeXchange.

Title	LC-MSMS of the lc4 MHC class I immunopeptidome
Description	MHC I-associated peptides (MAPs) presented at the surface of nucleated cells play a central role in CD8 T-cell immunosurveillance. MAPs presented by mature (i.e. MHC IIhi) medullary thymic epithelial cells (mTEChi) are essential to eliminate self-reactive CD8 T cells in a process called central tolerance. On tumor cells, MAPs that do not induce tolerance (i.e. non-tolerogenic MAPs), because absent from mTEChi or any other normal cells, are referred to as tumor-specific antigens (TSAs). Despite their clinical relevance, very few have been identified, even in highly mutated tumor types. Thus, we developed a novel proteogenomic workflow able to characterize the full TSA landscape of any tumor. Briefly, using RNA-seq data, we subtracted the mTEChi from the tumor signal to generate tumor-specific protein databases enriched in non-tolerogenic sequences. Using these databases to analyze the MAP repertoire of two murine cell lines (CT26 and EL4) sequenced by mass spectrometry, we identified a total of 21 TSAs, 90% of which derived from allegedly non-coding regions. Interestingly, our results highlighted that 70% of those TSAs derived from non-mutated yet tumor-restricted sequences, e.g. endogenous retroelements. Moreover, we showed that our approach is easily amenable to analyze human primary samples as we were able to identify TSAs in three lung tumor biopsies and four B-ALL specimens. Focusing on 5 TSAs, we demonstrated that both TSA expression and TSA-specific T-cell frequency in the pre-immune repertoire influenced the overall survival of pre-immunized tumor-bearing mice. In conclusion, this proof-of-concept study demonstrates that non-coding-derived TSAs are frequent and protective in vivo, while they could be shared by several individuals. Altogether, our findings will help expand the repertoire of human TSAs and facilitate their prioritization in the clinic.
HostingRepository	PRIDE
AnnounceDate	2018-10-22
AnnouncementXML	Submission_2018-12-11_06:56:51.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD009754
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Courcelles Mathieu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Deamidated; Oxidation
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-11 02:26:10	ID requested
1	2018-10-22 06:31:08	announced
⏵ 2	2018-12-11 06:56:52	announced	Updated publication reference for PubMed record(s): 30518613.

Laumont CM, Vincent K, Hesnard L, Audemard É, Bonneil É, Laverdure JP, Gendron P, Courcelles M, Hardy MP, C, ô, t, é C, Durette C, St-Pierre C, Benhammadi M, Lanoix J, Vobecky S, Haddad E, Lemieux S, Thibault P, Perreault C, Noncoding regions are the main source of targetable tumor-specific antigens. Sci Transl Med, 10(470):(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, lung cancer primary sample, LC-MSMS, MHC class I, immunopeptidome

Pierre Thibault
contact affiliation	Institute for Research in Immunology and Cancer, Department of Biochemistry, Department of Chemistry, Université de Montréal, Québec, Canada H3T 1J4
contact email	pierre.thibault@umontreal.ca
lab head
Courcelles Mathieu
contact affiliation	IRIC
contact email	mathieu.courcelles@umontreal.ca
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/2018/10/PXD009754

PRIDE project URI

• PRIDE
  1. PXD009754
     1. Label: PRIDE project
     2. Name: LC-MSMS of the lc4 MHC class I immunopeptidome