TOFIMS mass spectrometry-based immunopeptidomics refines tumor antigen identification

Naomi Hoenisch Gravel, Annika Nelde, Jens Bauer, Lena Mühlenbruch, Sarah M. Schroeder, Marian C. Neidert, Jonas Scheid, Steffen Lemke, Marissa L. Dubbelaar, Marcel Wacker, Anna Dengler, Reinhild Klein, Paul-Stefan Mauz, Hubert Löwenheim, Mathias Hauri-Hohl, Roland Martin, Jörg Hennenlotter, Arnulf Stenzl, Jonas S. Heitmann, Helmut R. Salih, Hans-Georg Rammensee and Juliane S. Walz ()
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Naomi Hoenisch Gravel: University and University Hospital Tübingen
Annika Nelde: University and University Hospital Tübingen
Jens Bauer: University and University Hospital Tübingen
Lena Mühlenbruch: University and University Hospital Tübingen
Sarah M. Schroeder: University and University Hospital Tübingen
Marian C. Neidert: University of Zürich and ETH Zürich
Jonas Scheid: University and University Hospital Tübingen
Steffen Lemke: University and University Hospital Tübingen
Marissa L. Dubbelaar: University and University Hospital Tübingen
Marcel Wacker: University and University Hospital Tübingen
Anna Dengler: University and University Hospital Tübingen
Reinhild Klein: University Hospital Tübingen
Paul-Stefan Mauz: University of Tübingen
Hubert Löwenheim: University of Tübingen
Mathias Hauri-Hohl: University Children’s Hospital Zürich
Roland Martin: University and University Hospital Zürich
Jörg Hennenlotter: University Hospital Tübingen
Arnulf Stenzl: University Hospital Tübingen
Jonas S. Heitmann: University of Tübingen
Helmut R. Salih: University of Tübingen
Hans-Georg Rammensee: University of Tübingen
Juliane S. Walz: University and University Hospital Tübingen

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based immunopeptidomics represents the only unbiased method for the direct identification and characterization of naturally presented tumor-associated peptides, a key prerequisite for the development of T cell-based immunotherapies. This study reports on the implementation of ion mobility separation-based time-of-flight (TOFIMS) MS for next-generation immunopeptidomics, enabling high-speed and sensitive detection of HLA-presented peptides. Applying TOFIMS-based immunopeptidomics, a novel extensive benignTOFIMS dataset was generated from 94 primary benign samples of solid tissue and hematological origin, which enabled the expansion of benign reference immunopeptidome databases with > 150,000 HLA-presented peptides, the refinement of previously described tumor antigens, as well as the identification of frequently presented self antigens and not yet described tumor antigens comprising low abundant mutation-derived neoepitopes that might serve as targets for future cancer immunotherapy development.

Date: 2023
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DOI: 10.1038/s41467-023-42692-7

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