MassIVE MSV000082848

Imported Reanalysis Dataset Public PXD002951

Sampling from proteome to HLA-DR ligandome

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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. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: HLA class II ; MHC class II ; ligandome ; ETD ; EThcD ; HCD

Contact

Principal Investigators:
(in alphabetical order) 		Dr Geert Mommen, Intravacc, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands, N/A
Submitting User: ccms

Publications

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. 2016 Apr;15(4):1412-23. Epub 2016 Jan 13.

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Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

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Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

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Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

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Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.