Immunopeptidomics Mapping of Listeria monocytogenes T Cell Epitopes in Mice

Mol Cell Proteomics. 2024 Sep;23(9):100829. doi: 10.1016/j.mcpro.2024.100829. Epub 2024 Aug 13.

Abstract

Listeria monocytogenes is a foodborne intracellular bacterial model pathogen. Protective immunity against Listeria depends on an effective CD8+ T cell response, but very few T cell epitopes are known in mice as a common animal infection model for listeriosis. To identify epitopes, we screened for Listeria immunopeptides presented in the spleen of infected mice by mass spectrometry-based immunopeptidomics. We mapped more than 6000 mouse self-peptides presented on MHC class I molecules, including 12 high confident Listeria peptides from 12 different bacterial proteins. Bacterial immunopeptides with confirmed fragmentation spectra were further tested for their potential to activate CD8+ T cells, revealing VTYNYINI from the putative cell wall surface anchor family protein LMON_0576 as a novel bona fide peptide epitope. The epitope showed high biological potency in a prime boost model and can be used as a research tool to probe CD8+ T cell responses in the mouse models of Listeria infection. Together, our results demonstrate the power of immunopeptidomics for bacterial antigen identification.

Keywords: Listeria monocytogenes; MHC; bacterial infection; epitope discovery; mass spectrometry.

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism
  • CD8-Positive T-Lymphocytes* / immunology
  • Epitope Mapping / methods
  • Epitopes, T-Lymphocyte* / immunology
  • Female
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Listeria monocytogenes* / immunology
  • Listeriosis* / immunology
  • Listeriosis* / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Peptides / immunology
  • Proteomics / methods
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Epitopes, T-Lymphocyte
  • Antigens, Bacterial
  • Peptides
  • Histocompatibility Antigens Class I
  • Bacterial Proteins