PXD002951

PXD002951 is an original dataset announced via ProteomeXchange.

Title	Sampling from proteome to HLA-DR ligandome
Description	Comprehensive analysis of the complex nature of the Human Leukocyte Antigen (HLA) class II ligandome is of utmost importance to understand the basis for CD4+ T cell mediated immunity and tolerance. Here, we implemented important improvements in the analysis of the repertoire of HLA-DR-presented peptides, using hybrid mass spectrometry-based peptide fragmentation techniques on a ligandome sample isolated from matured human monocyte-derived dendritic cells (DC). The reported data set constitutes nearly 14 thousand unique high-confident peptides, i.e. the largest single inventory of human DC derived HLA-DR ligands to date. From a technical viewpoint the most prominent finding is that no single peptide fragmentation technique could elucidate the majority of HLA-DR ligands, due to the wide range of physical chemical properties displayed by the HLA-DR ligandome. Our in-depth profiling allowed us to reveal a strikingly modest correlation between the abundance levels of surface-presented peptides and the cellular expression of their source proteins. Important selective sieving from the sampled proteome to the ligandome, was evidenced by specificity in the sequences of the core regions both at their N- and C- termini, hence not only reflecting binding motifs but also dominant protease activity associated to the endolysosomal compartments. Moreover, we demonstrate that the HLA-DR ligandome reflects a surface representation of cell-compartments specific for biological events linked to the maturation of monocytes into antigen presenting cells. Our results present new perspectives into the complex nature of the HLA class II system and will aid future immunological studies in characterizing the full breadth of potential CD4+ T cell epitopes relevant in health and disease.
HostingRepository	PRIDE
AnnounceDate	2016-10-27
AnnouncementXML	Submission_2016-10-27_04:00:40.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Geert Mommen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; amidated residue
Instrument	LTQ Orbitrap Elite; TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2015-09-21 02:55:46	ID requested
1	2016-01-25 15:48:25	announced
⏵ 2	2016-10-27 04:00:41	announced	Updated project metadata.

Mommen GP, Marino F, Meiring HD, Poelen MC, van Gaans-van den Brink JA, Mohammed S, Heck AJ, van Els CA, Sampling From the Proteome to the Human Leukocyte Antigen-DR (HLA-DR) Ligandome Proceeds Via High Specificity. Mol Cell Proteomics, 15(4):1412-23(2016) [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: HLA class II, MHC class II, ligandome, ETD, EThcD, HCD

Dr Geert Mommen
contact affiliation	Intravacc, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands
contact email	geertmommen@gmail.com
lab head
Geert Mommen
contact affiliation	Intravacc, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands
contact email	geertmommen@gmail.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/2016/01/PXD002951

PRIDE project URI

• PRIDE
  1. PXD002951
     1. Label: PRIDE project
     2. Name: Sampling from proteome to HLA-DR ligandome