title: Antagonistic variant virus prevents wild-type virus-induced lethal immunopathology.
abstract: Altered peptide ligands (APLs) and their antagonistic or partial agonistic character-influencing T cell activation have mainly been studied in vitro Some studies have shown APLs as a viral escape mechanism from cytotoxic CD8(+) T cell responses in vivo. However, whether infection or superinfection with a virus displaying an antagonistic T cell epitope can alter virus-host relationships via inhibiting T cell-mediated immunopathology is unclear. Here, we evaluated a recently described CD4(+) T cell escape lymphocytic choriomeningitis virus (LCMV) variant that in vitro displayed antagonistic characteristics for the major histocompatibility complex class II-restricted mutated epitope. Mice transgenic for the immunodominant LCMV-specific T helper epitope that usually succumb to wild-type LCMV-induced immunopathology, survived if they were simultaneously coinfected with antagonistic variant but not with control virus. The results illustrate that a coinfecting APL-expressing virus can shift an immunopathological virus-host relationships in favor of host survival. This may play a role in poorly cytopathic long-lasting virus carrier states in humans.
authors.affiliation: Institute for Experimental Immunology, University Hospital, CH-8091 Zurich, Switzerland. hunziker@pathol.unizh.ch
authors.forename: Lukas
authors.initials: L
authors.lastname: Hunziker
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.forename: Adrian
authors.initials: A
authors.lastname: Ciurea
authors.forename: Marianne M A
authors.initials: MM
authors.lastname: Martinic
authors.forename: Bernhard
authors.initials: B
authors.lastname: Odermatt
authors.forename: Hans
authors.initials: H
authors.lastname: Hengartner
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002469:Cell Separation; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008212:Lymphocyte Depletion; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell