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Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes
14:05

Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes

Published on: September 20, 2013

CTL epitope generation is tightly linked to cellular proteolysis of a Listeria monocytogenes antigen

A J Sijts1, M S Villanueva, E G Pamer

  • 1Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|February 15, 1996
PubMed

Insights

Proteasomes play a crucial role in breaking down Listeria monocytogenes proteins for immune presentation. Inhibiting proteasomes blocks the generation of key cytotoxic T lymphocyte (CTL) epitopes.

Area of Science:

  • Immunology
  • Bacteriology
  • Proteasome Biology

Background:

  • Listeria monocytogenes is an intracellular pathogen.
  • Host cells process bacterial proteins into peptides for immune surveillance.
  • Cytotoxic T Lymphocytes (CTLs) recognize these peptides presented by MHC class I molecules.

Purpose of the Study:

  • To investigate the role of cytosolic proteolysis in the generation of CTL epitopes from Listeria monocytogenes p60 protein.
  • To determine if proteasomes are involved in the initial degradation of bacterial antigens.

Main Methods:

  • Infection of host cells with Listeria monocytogenes.
  • Treatment of infected cells with proteasome inhibitors (LLnL and Z-LLF).
  • Acid elution, HPLC purification, and quantification of specific p60-derived peptides (p60 217-225 and p60 449-457).

Main Results:

  • Proteasome inhibitors completely blocked the degradation of cytosolic p60.
  • A direct correlation was observed between p60 degradation and the generation of p60-derived epitopes.
  • The inhibitors exhibited differential effects on the generation of the two specific CTL epitopes.

Conclusions:

  • Proteasomes are implicated in the early stages of antigen degradation.
  • Distinct proteolytic pathways may generate different CTL epitopes from the same antigen.

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