The amino acid sequence YPHFMPTNL of pp89, the -encoded product of murine cytomegalovirus (MCMV; Smith strain), constitutes an immunodominant T cell epitope recognized in association with H-2L. Nucleotide sequencing of MCMV isolates derived from wild mice identified variation between amino acids 147–192 of pp89 in 19 of 27 isolates, including the region encompassing the CTL epitope (amino acid residues 168–176). Four groups of isolates with naturally occurring variant sequences for the CTL epitope were defined: (1) YPHFMPNL; (2) YPHFMPL; (3) YPHFPL; and (4) YFMPNL. The remaining isolates, and the laboratory strains K181 and Vancouver, showed complete identity with the Smith strain. Polyclonal pp89 (Smith strain)-specific CTL only weakly recognized target cells infected with MCMV from most variant groups. No lysis of cells infected with isolate N1 from group 4 was detected. Analyses of cross-reactive recognition of YPHFMPTNL peptide-coated targets by CTL primed with variant MCMV isolates showed that the group 2 and 3 isolates, G4 and K6, respectively, but not the group 4 isolate N1, elicited CTL that exhibited a cross-reactive response. Furthermore, while the group 2 and 3 isolates G4 and K6 were able to prime CTL responses that displayed reactivity to homologous pp89 variant nonapeptides, the group 4 isolate N1 failed to do so. Finally, while immunization of mice with the nonapeptide YPHFMPTNL conferred significant protection against the laboratory strain KI81, no evidence of protection was observed for the group 2 and 4 variants G4 and N1, respectively. These observations raise the possibility that clinical isolates of HCMV may also differ in sequence from potential vaccine strains at immunodominant epitopes for CD8 T cells thus reducing the efficacy of vaccination.


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