PXD000450

PXD000450 is an original dataset announced via ProteomeXchange.

Title	HLA-B40-peptidome
Description	HLA class I molecules bind peptides derived from the intracellular degradation of endogenous proteins and present them to cytotoxic T lymphocytes, allowing the immune system to detect transformed or virally infected cells. It is known that endogenous HLA class I associated peptides may harbor posttranslational modifications. In particular, phosphorylated ligands have raised much interest as potential targets for cancer immunotherapy. By combining affinity purification with high resolution mass spectrometry, we identified more than 2000 unique ligands associated to HLA-B40. Sequence analysis revealed two major anchor motifs: Aspartic or glutamic acid at peptide position 2 (P2) and methionine, phenylalanine or aliphatic residues at the C-terminus. The use of IMAC and TiO2 affinity chromatography allowed the characterization of 86 phosphorylated ligands. Every sequence belonging to this subset was further confirmed by comparing its experimental MS2 spectrum with that obtained upon fragmentation of the corresponding synthetic peptide. Remarkably, three of the identified phospholigands lacked a canonical anchor residue at P2 containing phosphoserine instead. Binding assays showed that this sort of peptides bound to HLA-B40 with high affinity probably due to the molecular mimicry between these residues. Altogether, our data demonstrate that the peptide repertoire of a given HLA allotype can be broadened by the presentation of peptides with posttranslational modifications at major anchor positions. We suggest that ligands with phosphorylated residues at P2 may be optimal targets for T-cell based cancer immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2017-10-24
AnnouncementXML	Submission_2017-10-24_04:58:34.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD000450
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Miguel Marcilla
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; deaminated residue
Instrument	instrument model: TripleTOF 5600; TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2013-09-04 13:25:36	ID requested
1	2014-02-03 02:33:43	announced
2	2014-07-28 00:46:32	announced	Updated project metadata.
3	2016-10-27 04:00:28	announced	Updated project metadata.
4	2016-11-09 02:55:59	announced	Updated project metadata.
⏵ 5	2017-10-24 04:58:35	announced	Updated project metadata.

Marcilla M, Alp, í, zar A, Lombard, í, a M, Ramos-Fernandez A, Ramos M, Albar JP, Increased diversity of the HLA-B40 ligandome by the presentation of peptides phosphorylated at their main anchor residue. Mol Cell Proteomics, 13(2):462-74(2014) [pubmed]

ProteomeXchange project tag: Human Immuno-Peptidome Project (HUPO-HIPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

curator keyword: Biomedical

submitter keyword: peptidome, HLA, phosphopeptidome, HLA-B40,MHC

Miguel Marcilla
contact affiliation	Proteomics Unit - Dpt. of Macromolecular Structures - Spanish National Biotechnolgy Centre (CNB-CSIC)
contact email	mmarcilla@cnb.csic.es
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/2014/02/PXD000450

PRIDE project URI

• PRIDE
  1. PXD000450
     1. Label: PRIDE project
     2. Name: HLA-B40-peptidome