PXD056652-1

PXD056652 is an original dataset announced via ProteomeXchange.

Title	Determining TCR Binding Orientation and Peptide-HLA Interac-tions Using Cross-Linking Mass Spectrometry
Description	T cell receptors (TCRs) recognize specific peptides presented by human leukocyte antigens (HLAs) on the surface of antigen presenting cells and are involved in fighting pathogens and cancer surveillance. Canonical docking orientation of TCRs to their target peptide-HLAs (pHLAs) is essential for T cell activation, with reverse binding TCRs lacking functionality. TCR binding geometry and molecular interaction footprint with pHLAs is typically obtained by determining the crystal structure. Here, we describe the use of a cross-linking tandem mass spectrometry (XL-MS/MS) method to decipher the binding orienta-tion of several TCRs to their target pHLAs. Cross-linking sites were localized to specific residues and their molecular interac-tions showed differentiation between TCRs binding in canonical or reverse orientations. Structural prediction and crystal structure determination of two TCR-pHLA complexes validated these findings. The XL-MS/MS method described herein offers a faster and simpler approach for elucidating TCR-pHLA binding orientation and interactions.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_03:26:28.379.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Powell
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-09 05:17:58	ID requested
⏵ 1	2025-05-07 03:26:29	announced

10.1016/j.jbc.2025.108445;

Powell T, Karuppiah V, Shaikh SA, Pengelly R, Mai N, Barnbrook K, Sharma A, Harper S, Ebner M, Creese AJ, Determining T-cell receptor binding orientation and Peptide-HLA interactions using cross-linking mass spectrometry. J Biol Chem, 301(5):108445(2025) [pubmed]

submitter keyword: LC-MS/MS, Cross-linking

Thomas Powell
contact affiliation	Immunocore Ltd.
contact email	thomas.powell@immunocore.com
lab head
Thomas Powell
contact affiliation	Immunocore
contact email	thomas.powell@immunocore.com
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/2025/05/PXD056652

PRIDE project URI

• PRIDE
  1. PXD056652
     1. Label: PRIDE project
     2. Name: Determining TCR Binding Orientation and Peptide-HLA Interac-tions Using Cross-Linking Mass Spectrometry