PXD033232-2

PXD033232 is an original dataset announced via ProteomeXchange.

Title	Deciphering the immunopeptidome in vivo reveals novel tumor antigens
Description	Effective immunosurveillance of cancer requires the presentation of peptide antigens on major histocompatibility complex Class I (MHC-I). Recent developments in proteomics have improved the identification of peptides that are naturally presented by MHC-I, collectively known as the “immunopeptidome”. Current approaches to profile tumor immunopeptidomes have been limited to in vitro investigation, which fails to capture the in vivo repertoire of MHC-I peptides, or bulk tumor lysates, which are obscured by the lack of cancer cell-specific MHC-I isolation. To overcome these limitations, we report here the engineering of a Cre recombinase-inducible affinity tag into the endogenous mouse MHC-I gene and targeting of this allele to the KrasLSL-G12D/+; p53fl/fl (KP) mouse model (KP/KbStrep). This novel approach has allowed us to precisely isolate MHC-I peptides from autochthonous pancreatic ductal adenocarcinoma (PDAC) and lung adenocarcinoma (LUAD) in vivo. With this powerful analytical tool, we were able to profile the evolution of the LUAD immunopeptidome from the alveolar type 2 cell-of-origin through late-stage disease. Differential peptide presentation in LUAD is not driven by increased mRNA expression or translation rate and is likely driven by post-translational mechanisms. Vaccination of mice with peptides presented by LUAD in vivo provoked CD8 T-cell responses in naïve and tumor bearing mice. Many peptides unique to LUAD, including immunogenic peptides, exhibited very low expression of the cognate mRNA provoking reconsideration of antigen prediction pipelines that triage peptides according to transcript abundance. Beyond cancer, the KbStrep allele is compatible with a broad range of Cre-driver lines to explore antigen presentation in vivo in the pursuit of understanding basic immunology, infectious disease, and autoimmunity.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:01:06.141.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD033232
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ryuhjin Ahn
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Exploris 480; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-14 04:48:58	ID requested
1	2022-06-20 04:49:45	announced
⏵ 2	2023-11-14 09:01:09	announced	2023-11-14: Updated project metadata.

Jaeger AM, Stopfer LE, Ahn R, Sanders EA, Sandel DA, Freed-Pastor WA, Rideout WM, Naranjo S, Fessenden T, Nguyen KB, Winter PS, Kohn RE, Westcott PMK, Schenkel JM, Shanahan SL, Shalek AK, Spranger S, White FM, Jacks T, Deciphering the immunopeptidome in vivo reveals new tumour antigens. Nature, 607(7917):149-155(2022) [pubmed]

submitter keyword: H2-Kb, in vivo, ligandomics,MHC, immunopeptidomics, antigen presentation

Forest White
contact affiliation	Department of Biological Engineering, Massachusetts Institute of Technology
contact email	fwhite@mit.edu
lab head
Ryuhjin Ahn
contact affiliation	Massachusetts Institute of Technology
contact email	ryuhjin.ahn@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033232
     1. Label: PRIDE project
     2. Name: Deciphering the immunopeptidome in vivo reveals novel tumor antigens