title: Virus-specific CTL responses induced by an H-2K(d)-restricted, motif-negative 15-mer peptide from the fusion protein of respiratory syncytial virus.
abstract: We describe 15-mer peptide P8:F92-106 from the F protein of respiratory syncytial virus (RSV) that can act as an MHC class I-restricted (H-2K(d)) epitope for RSV-specific CD8(+) CTL. This peptide is interesting because not only is it the first murine CTL epitope to be identified in the F protein but also because it does not contain a known allele-specific motif, as all 15 amino acids appear to be required for effective presentation to CTL. In in vitro MHC class I refolding experiments, peptide P8:F92-106 induced complex formation with H-2K(d) heavy chains and beta2-microglobulin. Immunization of BALB/c mice with P8:F92-106 resulted in the induction of peptide and RSV-specific CTL responses as well as peptide-specific proliferative responses. Following intranasal challenge with RSV, P8:F92-106-immunized mice showed a significant reduction in viral load in the lungs compared to that seen in unimmunized mice. Furthermore, passive transfer of purified CD8(+) lymphocytes into BALB/c scid mice prior to challenge with RSV also resulted in a reduction in the virus load in lungs of challenged mice. These results indicate the potential of synthetic peptide epitopes for the induction of protective immune responses against RSV infection.
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK1.
authors.forename: Shisong
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK1.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Borthwick
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK1.
authors.forename: Paul
authors.initials: P
authors.lastname: Morrison
authors.affiliation: Laboratory of Molecular Medicine, Children's Hospital, Boston MA 02115, USA2.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK1.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Steward
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010455:Peptides; D022261:Respiratory Syncytial Virus Vaccines; D014764:Viral Proteins