title: CTL escape viral variants. II. Biologic activity in vivo.
abstract: The proteins of lymphocytic choriomeningitis virus (LCMV) contain only three known peptide regions that are processed and then held in place by the MHC class I H-2b (Db) glycoprotein on the cell's surface for recognition by LCMV-specific Db-restricted cytotoxic T lymphocytes (CTL). These peptides are from the glycoprotein (GP), amino acids 33-41 KAVYNFATC (GP1) and 276-286 SGVENPGGYCL (GP2), and the nucleoprotein (NP), 396-404. We have used CTL clones that recognized only GP1, GP2, and NP to select viral variants that upon infecting cells bearing H-2b molecules escaped recognition by virus-specific CTL directed against the viral GP (GP1 + GP2) mutant, termed GPV, or the viral GP and NP (GP1 + GP2 + NP) mutant, termed GPV+NPV. These CTL "escape" variants nevertheless elicited sufficient host-protective activity in vivo to abort acute infection and prevent the occurrence of persistent infection. This protection was CD8+ lymphocyte mediated and associated with the generation of a novel (for H-2b mice) CTL response to the viral L protein. Hence CTL epitopes form a hierarchy, in which responses to "weak" epitopes are suppressed in the presence of "stronger" epitopes. Mutation in the strong epitopes may be of limited biological significance since the host can mount a protective response directed against the second level (weak) epitopes.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Lewicki
authors.forename: M G
authors.initials: MG
authors.lastname: Von Herrath
authors.forename: C F
authors.initials: CF
authors.lastname: Evans
authors.forename: J L
authors.initials: JL
authors.lastname: Whitton
authors.forename: M B
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins