title: CTL epitopes identified with a defective recombinant adenovirus expressing measles virus nucleoprotein and evaluation of their protective capacity in mice.
abstract: Cytotoxic T-lymphocyte (CTL) responses to measles virus (MV) play an important role in recovery from infection, with one of the major target proteins for CTL activity being the nucleoprotein (Np). In this report, a replication-deficient adenovirus-5 recombinant, expressing for MV Np (Rad68) was tested for in vivo priming of MV Np-specific CTL responses in BALB/c and CBA mice. In both strains of mice strong Np-specific CTL responses were induced and these responses were shown to be MHC class I restricted. Using overlapping 15mer peptides spanning residues 1-505 of MV Np a single epitope comprising residues 281-295 was identified in BALB/c mice whereas, in CBA mice two epitopes comprising residues 51-65 and 81-95, were identified. These epitopes were found to contain class I motifs for H-2L(d) and H-2K(k) MHC molecules, respectively. Immunization of BALB/c and CBA mice with the respective CTL epitopes resulted in the in vivo induction of peptide-and MV Np-specific CTL responses. In addition, the identified H-2K(k) restricted CTL epitopes conferred some protection against encephalitis induced following intracerebral challenge with a lethal dose of canine distemper virus (the Np of which shares 70% sequence homology with MV Np). These findings highlight the potential of using well-defined CTL epitopes to control virus infection.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK.
authors.forename: E B
authors.initials: EB
authors.lastname: Schadeck
authors.forename: C D
authors.initials: CD
authors.lastname: Partidos
authors.forename: A R
authors.initials: AR
authors.lastname: Fooks
authors.forename: O E
authors.initials: OE
authors.lastname: Obeid
authors.forename: G W
authors.initials: GW
authors.lastname: Wilkinson
authors.forename: J R
authors.initials: JR
authors.lastname: Stephenson
authors.forename: M W
authors.initials: MW
authors.lastname: Steward
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004216:Distemper / Q000401:mortality / Q000517:prevention & control; D004217:Distemper Virus, Canine / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008459:Measles virus / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology / Q000378:metabolism*; D019151:Peptide Library; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D019151:Peptide Library; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus