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Updated: Aug 9, 2026

Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses
Published on: November 16, 2016
MHC class I antigen processing of Listeria monocytogenes proteins: implications for dominant and subdominant CTL
E G Pamer1, A J Sijts, M S Villanueva
1Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520, USA.
Insights
The MHC class I antigen-processing pathway efficiently generates epitopes for cytolytic T lymphocytes (CTL). However, the prevalence of antigens or epitopes does not predict the strength of the immune response to Listeria monocytogenes.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Listeria monocytogenes (L. monocytogenes) secretes virulence proteins into host cell cytosol.
- These proteins are processed by host proteasomes and presented by MHC class I molecules.
Purpose of the Study:
- To investigate the efficiency of MHC class I antigen processing and epitope generation.
- To determine the relationship between epitope prevalence and the magnitude of the in vivo CTL response.
Main Methods:
- Analysis of antigen processing by the MHC class I pathway.
- Quantification of epitope generation from L. monocytogenes antigens.
- Assessment of cytolytic T lymphocyte (CTL) responses in infected mice.
Main Results:
- The MHC class I antigen-processing pathway is highly efficient in generating T cell epitopes.
- A significant percentage of degraded antigens (3-30%) are processed into MHC class I-bound nonamer peptides.
- The immunodominant CTL response is primed by a low-prevalence epitope from a minimally detectable antigen.
Conclusions:
- Epitope generation efficiency and prevalence alone do not predict the magnitude of T cell responses.
- Additional, currently unknown factors influence the development of immunodominant and subdominant T cell responses during L. monocytogenes infection.
Abstract:
Listeria monocytogenes (L. monocytogenes) secretes proteins associated with its virulence into the cytosol of infected cells. These secreted proteins are degraded by host cell proteasomes and processed into peptides that are bound by MHC class I molecules in the endoplasmic reticulum. We have found that the MHC class I antigen-processing pathway is very efficient at generating the epitopes that are presented to cytolytic T lymphocytes (CTL). Depending on which antigen is investigated, from 3 to 30% of degraded antigens are processed into nonamer peptides that are bound by MHC class I molecules. Surprisingly, neither the efficiency of epitope generation nor the absolute number of epitopes per infected cell determines the magnitude of the in vivo CTL response. One of the least prevalent epitopes, derived from an antigen that is virtually undetectable in infected cells, primes the immunodominant CTL response in L. monocytogenes-infected mice. Our studies suggest that immunodominant and subdominant T-cell responses cannot be predicted by the prevalence of antigens or epitopes alone, and that additional factors, yet to be determined, are involved.
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