ANALYSIS OF THE CONTRIBUTION OF CTL EPITOPES IN THE IMMUNOBIOLOGY OF MORBILLIVIRUS INFECTION

In Balb/c (H-2(d)) 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 invest igate whether this epitope is immunologically effective when it is pre sent within the primary sequence of a nonviral protein, we have incorp orated the 281-289 motif into the human CD36 protein. When cells are i nfected 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 protecte d mice from a lethal dose of CDV, but did not block virus replication. The MVNP contains four other potential L(d)-restricted motifs. To inv estigate if these could be utilized in the absence of the dominant epi tope, 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 vacc inated with VV-NP F289S they were only partially protected from a leth al CDV challenge. The significance of these results for MV vaccine dev elopment is discussed. (C) 1996 Academic Press, Inc.