1. TOF IMS mass spectrometry-based immunopeptidomics refines tumor antigen identification.
- Author
-
Hoenisch Gravel N, Nelde A, Bauer J, Mühlenbruch L, Schroeder SM, Neidert MC, Scheid J, Lemke S, Dubbelaar ML, Wacker M, Dengler A, Klein R, Mauz PS, Löwenheim H, Hauri-Hohl M, Martin R, Hennenlotter J, Stenzl A, Heitmann JS, Salih HR, Rammensee HG, and Walz JS
- Subjects
- Humans, Antigens, Neoplasm, Mass Spectrometry methods, HLA Antigens, Peptides chemistry, Histocompatibility Antigens Class II, Histocompatibility Antigens Class I, Neoplasms therapy
- 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 (TOF
IMS ) 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., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF