title: Protective efficacy of individual CD8+ T cell specificities in chronic viral infection.
abstract: Specific CD8(+) T cells (CTLs) play an important role in resolving protracted infection with hepatitis B and C virus in humans and lymphocytic choriomeningitis virus (LCMV) in mice. The contribution of individual CTL specificities to chronic virus control, as well as epitope-specific patterns in timing and persistence of antiviral selection pressure, remain, however, incompletely defined. To monitor and characterize the antiviral efficacy of individual CTL specificities throughout the course of chronic infection, we coinoculated mice with a mixture of wild-type LCMV and genetically engineered CTL epitope-deficient mutant virus. A quantitative longitudinal assessment of viral competition revealed that mice continuously exerted CTL selection pressure on the persisting virus population. The timing of selection pressure characterized individual epitope specificities, and its magnitude varied considerably between individual mice. This longitudinal assessment of "antiviral efficacy" provides a novel parameter to characterize CTL responses in chronic viral infection. It demonstrates remarkable perseverance of all antiviral CTL specificities studied, thus raising hope for therapeutic vaccination in the treatment of persistent viral diseases.
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland; World Health Organization Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva 4, Switzerland;
authors.forename: Susan
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria;
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergthaler
authors.affiliation: Center for Modeling and Simulation in the Biosciences, BioQuant-Center, Heidelberg University, 69120 Heidelberg, Germany; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87544; Institute of Integrative Biology, ETH Zurich, 8092 Zurich, Switzerland;
authors.forename: Frederik
authors.initials: F
authors.lastname: Graw
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland; Department of Dermatology, University Hospital of Lausanne, 1011 Lausanne, Switzerland; and.
authors.forename: Lukas
authors.initials: L
authors.lastname: Flatz
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland; World Health Organization Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva 4, Switzerland; Division of Experimental Virology, Department of Biomedicine, University of Basel, 4009 Basel, Switzerland.
authors.forename: Weldy V
authors.initials: WV
authors.lastname: Bonilla
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland; World Health Organization Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva 4, Switzerland;
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland; World Health Organization Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva 4, Switzerland;
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Lambert
authors.affiliation: Institute of Integrative Biology, ETH Zurich, 8092 Zurich, Switzerland;
authors.forename: Roland R
authors.initials: RR
authors.lastname: Regoes
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland; World Health Organization Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva 4, Switzerland; Division of Experimental Virology, Department of Biomedicine, University of Basel, 4009 Basel, Switzerland Daniel.Pinschewer@gmx.ch.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Pinschewer
mesh_terms: D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte