Dataset Information

Digital mapping of immunopeptidomes

ABSTRACT: We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.

INSTRUMENT(S): LTQ Orbitrap, TripleTOF 5600, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, T Cell, Peripheral Blood Mononuclear Cell, Cell Culture

SUBMITTER: Etienne Caron

LAB HEAD: Ruedi Aebersold

PROVIDER: PXD001872 | Pride | 2015-07-14

REPOSITORIES: Pride

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Publications

An open-source computational and data resource to analyze digital maps of immunopeptidomes.

Caron Etienne E Espona Lucia L Kowalewski Daniel J DJ Schuster Heiko H Ternette Nicola N Alpízar Adán A Schittenhelm Ralf B RB Ramarathinam Sri H SH Lindestam Arlehamn Cecilia S CS Chiek Koh Ching C Gillet Ludovic C LC Rabsteyn Armin A Navarro Pedro P Kim Sangtae S Lam Henry H Sturm Theo T Marcilla Miguel M Sette Alessandro A Campbell David S DS Deutsch Eric W EW Moritz Robert L RL Purcell Anthony W AW Rammensee Hans-Georg HG Stevanovic Stefan S Aebersold Ruedi R

eLife 20150708

We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first ...[more]

PMID: 26154972

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Project description:Biomaterials play an increasing role in clinical applications and regenerative medicine. Modern biomaterials should imitate the function of damaged tissue without triggering an immune response, initiate self-regeneration of the body and gradually degrade after implantation. The immune system is now well recognized to play a major role in influencing the biocompatibility of implanted medical devices. To develop a better understanding of the effects of biomaterials on the immune response, we have developed a highly sensitive novel test system capable of examining changes in the immune system by biomaterial. Here, we evaluate for the first time the immunopeptidome, a highly sensitive system that reflects cancer transformation, virus or drug influences and passes these changes directly to T cells, as a test system to examine the effects of contact with materials. Since monocytes are one of the first immune cells reacting to biomaterials, we have tested the influence of different materials - stainless steel, aluminum, zinc, high-density polyethylene, polyurethane films containing zinc diethyldithiocarbamate, copper, and zinc sulphate - on the monocytic THP-1 cell line. Material-associated peptides were identified after stimulation with all material types examined. The magnitude of induced changes in the immunopeptidome after the stimulation appears comparable to that of bacterial lipopolysaccharides (LPS). The source proteins of many detected peptides are associated with cytotoxicity, fibrosis, autoimmunity, inflammation and cellular stress. Considering all tested materials, it was found that the LPS-induced cytotoxicity-, inflammation- and cellular stress-associated HLA class I peptides were mainly induced by aluminum and HLA class II peptides mainly by stainless steel. These findings provide some of the first insights into the effects on the immunopeptidome by biomaterials. A more thorough understanding of these effects may enable the design of more biocompatible implant materials using in vitro models in future. This may be achieved through developing a deeper understanding of possible immune responses induced by biomaterials such as fibrosis, inflammation, cytotoxicity, and autoimmune reactions.

Dataset Information

Digital mapping of immunopeptidomes

Publications

An open-source computational and data resource to analyze digital maps of immunopeptidomes.

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