Analysis of the contribution of CTL epitopes in the immunobiology of morbillivirus infection.
In Balb/c (H-2d) mice, the nucleoprotein (NP) of measles virus (MV) induces a MHC class I restricted-CTL response to a single 9-amino-acid epitope (aa 281--289). This L(d)-restricted epitope is also present in the NP of the closely related canine distemper virus (CDV). To investigate whether this epitope is immunologically effective when it is present within the primary sequence of a nonviral protein, we have incorporated the 281--289 motif into the human CD36 protein. When cells are infected with vaccinia virus (VV) recombinants expressing this protein, CD36NP, the MV epitope is correctly processed and the cells are lysed by MVNP-specific CTLs. In vivo, VV-CD36NP induced CTLs which protected mice from a lethal dose of CDV, but did not block virus replication. The MVNP contains four other potential L(d)-restricted motifs. To investigate if these could be utilized in the absence of the dominant epitope, a mutant NP was produced in which one of the anchor residues in the aa 281--289 motif was mutated. Cells infected with a VV recombinant expressing this protein (VV-NP F289S) were only poorly lysed by MVNP-specific CTLs. Similarly, immunization of Balb/c mice with VV-NP F289S induced a lower level of CTL activity compared to the VV-NP, but the activity was now directed to three other epitopes. When mice were vaccinated with VV-NP F289S they were only partially protected from a lethal CDV challenge. The significance of these results for MV vaccine development is discussed.
Beauverger
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P
INSERM Unit 404 "Immunity and Vaccination," Institut Pasteur de Lyon, France.
Cardoso
A I
AI
Daviet
L
L
Buckland
R
R
Wild
T F
TF
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D004279:DNA, Viral; D004216:Distemper / Q000276:immunology / Q000517:prevention & control; D004217:Distemper Virus, Canine / Q000276:immunology; D004285:Dogs; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D018955:CD36 Antigens; D004279:DNA, Viral; D000939:Epitopes; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines; C058314:nucleoprotein, Measles virus