1. Influence of a single viral epitope on T cell response and disease after infection of mice with respiratory syncytial virus.
- Author
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Vallbracht S, Jessen B, Mrusek S, Enders A, Collins PL, Ehl S, and Krempl CD
- Subjects
- Amino Acid Sequence, Amino Acid Substitution, Animals, Epitopes, T-Lymphocyte genetics, Immunodominant Epitopes genetics, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Oligopeptides immunology, Receptors, Antigen, T-Cell metabolism, Respiratory Syncytial Virus Infections genetics, Epitopes, T-Lymphocyte immunology, Immunodominant Epitopes immunology, Respiratory Syncytial Virus Infections immunology, Respiratory Syncytial Viruses immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
CTL are important for virus clearance but also contribute to immunopathology after the infection of BALB/c mice with respiratory syncytial virus (RSV). The pulmonary immune response to RSV is dominated by a CTL population directed against the CTL epitope M2-1 82-90. Infection with a virus carrying an M2-1 N89A mutation introduced by reverse genetics failed to activate this immunodominant CTL population, leading to a significant decrease in the overall antiviral CTL response. There was no compensatory increase in responses to the mutated epitope, to the subdominant epitope F 85-93, or to yet undefined minor epitopes in the N or the P protein. However, there was some increase in the response to the subdominant epitope M2-1 127-135, which is located in the same protein and presented by the same H-2Kd MHC molecule. Infection with the mutant virus reversed the oligoclonality of the T cell response elicited by the wild-type virus. These changes in the pattern and composition of the antiviral CTL response only slightly impaired virus clearance but significantly reduced RSV-induced weight loss. These data illustrate how T cell epitope mutations can influence the virus-host relationship and determine disease after an acute respiratory virus infection. more...
- Published
- 2007
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