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Published on: June 22, 2016
Cytotoxic T cell response to Mengo virus in mice: effector cell phenotype and target proteins
N Escriou1, C Leclerc, S Gerbard
1Unité de Virologie Moléculaire, URA CNRS#1966, Institut Pasteur, Paris, France.
Insights
Mengo virus infection elicits a CD8+ cytotoxic T lymphocyte (CTL) response restricted by MHC class I. This immune response primarily targets the VP2 protein, indicating its immunodominance in controlling viral infection.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Cytotoxic T lymphocytes (CTLs) are crucial for controlling viral infections.
- Understanding the specific viral antigens recognized by CTLs is essential for vaccine development.
Purpose of the Study:
- To investigate the cytotoxic T lymphocyte (CTL) response to Mengo virus infection.
- To identify the specific Mengo virus capsid proteins recognized by CD8+ T cells.
- To determine the immunodominant epitope(s) targeted by the CTL response.
Main Methods:
- Mice were infected with an attenuated Mengo virus strain.
- CTL activity was measured in spleen cell cultures after in vitro stimulation.
- Recombinant vaccinia viruses expressing Mengo virus capsid proteins (VP0, VP1, VP3) were used.
- MHC class I restriction and CD8+ T cell mediation were confirmed.
- Cold target inhibition assays were performed.
Main Results:
- High CTL activity was detected in infected mice.
- The CTL response was MHC class I-restricted and CD8+ T cell-mediated.
- Only the VP0 capsid protein was recognized by CTLs.
- The immunodominant CTL epitope(s) were mapped to the VP2 protein (C-terminal half of VP0).
- VP0-expressing target cells almost completely inhibited lysis of Mengo virus-infected cells.
Conclusions:
- The CD8+ CTL response to Mengo virus is primarily directed against the VP2 protein.
- VP2 is the immunodominant antigen recognized by CTLs in both C3H/HeJ and C57BL/6 mice.
- These findings provide insights into the T cell-mediated immune response against Mengo virus.
Abstract:
The Mengo virus specific cytotoxic T lymphocyte (CTL) response was investigated after intraperitoneal infection of mice with the attenuated Mengo virus strain vMC24. A high level of CTL activity was detected in spleen cell cultures obtained from infected C3H/HeJ (H-2k) or C57BL/6 (H-2b) mice after a secondary in vitro stimulation with Mengo virus-infected cells. The CTL activity, which was MHC class I-restricted, was shown to be mediated by CD8+ T cells. Recombinant vaccinia viruses that expressed capsid proteins VP0, VP1 or VP3 were produced and used to identify the protein(s) recognized by the Mengo virus-specific CTLs. In both C3H/HeJ and C57BL/6 mice, analysis of CTL activity against target cells expressing each capsid protein showed that VP0 was the only capsid protein recognized by the CD8+ CTLs. The CTL epitope(s) could be further located in the C-terminal half of VP0, i.e. in capsid protein VP2. Moreover, using unlabelled target cells expressing VP0 as cold competitors, we were able to almost completely inhibit recognition and lysis of Mengo virus-infected cells by specific CD8+ CTLs. Thus, the CTL response directed against VP2 was immunodominant in both C3H/HeJ- and C57BL/6-infected mice.
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