Virus-specific CTL responses induced by an H-2K(d)-restricted, motif-negative 15-mer peptide from the fusion protein of respiratory syncytial virus.
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.
Jiang
Shisong
S
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK1.
Borthwick
Nicola J
NJ
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK1.
Morrison
Paul
P
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK1.
Gao
George F
GF
Laboratory of Molecular Medicine, Children's Hospital, Boston MA 02115, USA2.
Steward
Michael W
MW
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK1.
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*
D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010455:Peptides; D022261:Respiratory Syncytial Virus Vaccines; D014764:Viral Proteins