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Influence of a Single Viral Epitope on T Cell Response and Disease After Infection of Mice with Respiratory Syncytial Virus¹

Simone Vallbracht^*, Birthe Jessen^*, Sonja Mrusek^*, Anselm Enders^2,*, Peter L. Collins, Stephan Ehl^3,4,* and Christine D. Krempl^3,5,

^* Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Virology, Institute for Medical Microbiology and Hygiene, University Hospital Freiburg, Germany

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-2K^d 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Financial support was provided to S.E. by the Deutsche Forschungsgemeinschaft (SFB 620: TPA4). P.L.C. was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Intramural Research Program.

² Current address: Immunogenomics Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, Australia.

³ S.E. and C.D.K. contributed equally to this work.

⁴ Address correspondence and reprint requests to Dr. Stephan Ehl, Zentrum für Kinderheilkunde und Jugendmedizin, Mathildenstrasse 1, Freiburg, Germany. E-mail address: stephan.ehl{at}uniklinik-freiburg.de

⁵ Current address: Institute of Virology and Immunobiology, Julius-Maximilian University, Würzburg, Germany.

⁶ Abbreviations used in this paper: RSV, respiratory syncytial virus; BAL, bronchoalveolar lavage; LCMV, lymphocytic choriomeningitis virus; MOI, multiplicity of infection; rRSV, recombinant RSV; rVACV, recombinant vaccinia virus.