Absence of CTL responses to early viral antigens facilitates viral persistence.

Abstract

CD8+ T cells are crucial for the control of intracellular pathogens such as viruses and some bacteria. Using lymphocytic choriomeningitis virus (LCMV) infection of mice--the prototypic arenavirus evolutionarily closely related to human Lassa fever and South American hemorrhagic fever viruses, we have shown previously that the kinetics of Ag presentation determine immunodominance of the LCMV-specific CTL response due to progressive exhaustion of LCMV nucleoprotein (NP)-specific CTL upon increasing viral load. In this study, we provide evidence that CTL against early LCMV NP-derived epitopes are more important in virus control than those against late glycoprotein-derived epitopes. We show that mice that are tolerant to all NP-derived T cell epitopes are severely compromised in their ability to control larger inocula of LCMV, supporting our hypothesis that CD8+ T cells specific for early viral Ags play a major role in acute virus control. Thus, the kinetics with which virus-derived T cell epitopes are presented has a strong impact on the efficacy of the antiviral immunity. This aspect should be taken into consideration for the development of vaccines.

• Authors: Anita Schildknecht, Sarah Welti, Markus B Geuking, Lars Hangartner, Maries van den Broek
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 5 Pg. 3113-21 (Mar 01 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18292534 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Viral
• Epitopes, T-Lymphocyte
• Nucleoproteins
• Peptide Fragments
• nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus
• nucleoprotein peptide 394-408, lymphocytic choriomeningitis virus

Topics

• Animals
• Antigens, Viral (immunology)
• Cell Line, Tumor
• Cytotoxicity, Immunologic (genetics)
• Epitopes, T-Lymphocyte (immunology)
• Immune Tolerance (genetics)
• Lymphocytic Choriomeningitis (immunology, virology)
• Lymphocytic choriomeningitis virus (growth & development, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Nucleoproteins (immunology)
• Peptide Fragments (immunology)
• T-Lymphocytes, Cytotoxic (immunology, metabolism, virology)
• Viral Load