Influence of a single viral epitope on T cell response and disease after infection of mice with respiratory syncytial virus.
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.
Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany.
Simone
S
Vallbracht
Birthe
B
Jessen
Sonja
S
Mrusek
Anselm
A
Enders
Peter L
PL
Collins
Stephan
S
Ehl
Christine D
CD
Krempl
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009842:Oligopeptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell