EFFECT OF NATURAL SEQUENCE VARIATION AT THE H-2L(D)-RESTRICTED CD8(-CELL EPITOPE OF THE MURINE CYTOMEGALOVIRUS IE1-ENCODED PP89 ON T-CELL RECOGNITION() T)

The amino acid sequence YPHFMPTNL of pp89, the ie 1-encoded product of murine cytomegalovirus (MCMV; Smith strain), constitutes an immunodom inant T cell epitope recognized in association with H-2L(d), Nucleotid e sequencing of MCMV isolates derived from wild mice identified variat ion between amino acids 147-192 of pp89 in 19 of 27 isolates, includin g 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) YPHFMPPNL; (2) <YPHFMP(PS)under bar L>; (3) <YPHF(I)under bar P(PS)under bar L>; and (4) <Y(LD)under b ar FMP(P)under bar NL>. The remaining isolates, and the laboratory str ains K181 and Vancouver, showed complete identity with the Smith strai n, 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 crossreactive recognition of YPHFMPTNL peptide-coated targets by CTL p rimed with variant MCMV isolates showed that the group 2 and 3 isolate s, G4 and K6, respectively, but not the group 4 isolate N1, elicited C TL that exhibited a cross-reactive response, Furthermore, while the gr oup 2 and 3 isolates G4 and K6 were able to prime CTL responses that d isplayed reactivity to homologous pp89 variant nonapeptides, the group 4 isolate N1 failed to do so, Finally, while immunization of mice wit h the nonapeptide YPHFMPTNL conferred significant protection against t he laboratory strain K181, 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.