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

Significance Statement

Researchers from ETH Zürich have developed a new technology enabling the reproducible measurement of antigens (or peptides) presented to the immune system by major histocompatibility complex (MHC) molecules. This technology – known as SWATH mass spectrometry – could be used in the future to reproducibly detect and quantify immunogenic antigens and could therefore greatly help in the design of personalized immune-based therapies against infectious diseases and cancers.

Journal Reference

Elife. 2015 Jul 8;4. doi: 10.7554/eLife.07661.

Caron E¹, Espona L¹, Kowalewski DJ², Schuster H², Ternette N³, Alpízar A⁴, Schittenhelm RB⁵, Ramarathinam SH⁵, Lindestam Arlehamn CS⁶, Chiek Koh C¹,Gillet LC¹, Rabsteyn A², Navarro P⁷, Kim S⁸, Lam H⁹, Sturm T¹, Marcilla M⁴, Sette A⁶, Campbell DS¹⁰, Deutsch EW¹⁰, Moritz RL¹⁰, Purcell AW⁵, Rammensee HG², Stevanovic S², Aebersold R¹.

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¹Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zurich, Switzerland.

²Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.

³Target Discovery Institute Mass Spectrometry Laboratory, University of Oxford, Oxford, United Kingdom.

⁴Proteomics Unit, Spanish National Biotechnology Centre, Madrid, Spain.

⁵Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.

⁶La Jolla Institute for Allergy and Immunology, La Jolla, United States.

⁷Institute for Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

⁸Pacific Northwest National Laboratory, Richland, United States.

⁹Division of Biomedical Engineering and Department of Chemical and Biomolecular Engineering, Hong Kong University of Science and Technology, Hong Kong, China.

¹⁰Institute for Systems Biology, Seattle, United States.[/expand]

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.

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About the author

Etienne Caron was born in Canada. He did a Ph.D. in Systems Immunology at the University of Montreal where he worked on the analysis of the cellular immunopeptidomes. In 2013, he received a Marie Curie Intra-European Fellowship to carry out research in the group of Ruedi Aebersold in Switzerland. In 2015, he launched the HIPP (Human ImmunoPeptidomes Project) initiative as part of the Human Proteome Project. His current research focuses on how cutting edge technologies in mass spectrometry can be applied to identify and quantify MHC-associated peptides. Research on this topic will have an impact on the development of vaccines against infectious diseases and cancers.