PXD077352-1

PXD077352 is an original dataset announced via ProteomeXchange.

Title	Expanding the repertoire of chemically induced covalent neoantigens
Description	The ubiquitin-proteasome system (UPS) generates peptide fragments that are displayed on class I major histocompatibility complex (MHC-I) molecules. Hapten-modified peptides, which are derived from proteins covalently modified by exogenous small molecules, have long been proposed as a mechanism for immune recognition. Building on this concept, recent studies have begun to harness this mechanism for therapeutic purposes, demonstrating that covalent small molecules can engage this pathway to drive the presentation of hapten-modified peptide fragments, or covalent neoantigens. Here, we report a platform to systematically investigate this process and harness covalent neoantigens for immune cell recruitment and activation. Using bioorthogonal cysteine-reactive probes, we demonstrate that covalently modified intracellular proteins can be processed and presented as covalent neoantigens in multiple cell lines. Immunopeptidomics confirmed the presence of probe-modified peptides within the MHC-I immunopeptidome. We further integrated a bioorthogonal strategy for immune cell engagement by pairing methyltetrazine (mTz)-tagged covalent neoantigens with trans-cyclooctene (TCO)-conjugated immune cell recruiters, leading to the activation of CD32- and CD3-expressing reporter immune cells. These findings indicate an expanded scope of covalent neoantigen formation and provide a generalizable strategy for immune targeting of covalent neoantigens.
HostingRepository	PRIDE
AnnounceDate	2026-07-08
AnnouncementXML	Submission_2026-07-08_10:45:52.028.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaoyu Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-19 15:15:35	ID requested
⏵ 1	2026-07-08 10:45:52	announced

Dataset with its publication pending

submitter keyword: Immunopeptidomics, covalent neoantigens, MHC-I

Xiaoyu Zhang
contact affiliation	Northwestern University, Department of Chemistry
contact email	zhang@northwestern.edu
lab head
Xiaoyu Zhang
contact affiliation	Northwestern University
contact email	zhang@northwestern.edu
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/2026/07/PXD077352

PRIDE project URI

• PRIDE
  1. PXD077352
     1. Label: PRIDE project
     2. Name: Expanding the repertoire of chemically induced covalent neoantigens