TOFIMS mass spectrometry-based immunopeptidomics refines tumor antigen identification.

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.

• Authors: 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, Juliane S Walz
• Journal: Nature communications (Nat Commun) Vol. 14 Issue 1 Pg. 7472 (Nov 17 2023) ISSN: 2041-1723 [Electronic] England
• PMID: 37978195 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Histocompatibility Antigens Class I
• Antigens, Neoplasm
• HLA Antigens
• Peptides
• Histocompatibility Antigens Class II

Topics

• Humans
• Histocompatibility Antigens Class I
• Antigens, Neoplasm
• Mass Spectrometry (methods)
• HLA Antigens
• Neoplasms (therapy)
• Peptides (chemistry)
• Histocompatibility Antigens Class II