IMMUNODOMINANT MINK CELL FOCUS-INDUCING MURINE LEUKEMIA-VIRUS (MULV)-ENCODED CTL EPITOPE, IDENTIFIED BY ITS MHC CLASS-I-BINDING MOTIF, EXPLAINS MULV-TYPE SPECIFICITY OF MCF-DIRECTED CYTOTOXIC T-LYMPHOCYTES

H-2b mice are immunologic responders to the tumorigenic MCF1233 murine leukemia virus (MuLV), an AKV-related virus derived from endogenous C 57BL MuLV. We have identified an immunodominant CTL epitope that is ex pressed on MCF1233 MuLV-induced lymphomas of H-2b mice. C57BL/10 (B10) mice were immunized with an MCF1233-induced B10 B cell lymphoma, and tumor-specific CTL cultures were generated in vitro. These were tested for recognition of synthetic class I-binding MuLV peptides, selected for class I allele-specific motifs. One of 28 candidate peptides sensi tized target cells for CTL recognition. This peptide seems to be an im munodominant epitope, because it was recognized by all independent CTL clones, isolated from the tumor-specific bulk culture. The epitope (K SPWFTTL) is derived from the MCF1233 MuLV envelope (env)-p15E region a nd is shared by all endogenous AKV types of MuLV. It has an optimal le ngth of eight amino acids and is presented by the Kb H-2 class I molec ule. Interestingly, Friend, Moloney, and Rauscher (FMR) types of MuLV are not recognized by MCF MuLV-directed CTL. The FMR env-p15E proteins have a single amino acid difference at the first position of the MCF1 233 MuLV epitope (RSPWFTTL instead of KSPWFTTL). The corresponding FM R-encoded peptide bound class I H-2 K(b) equally well as the MCF pepti de, but it was poorly recognized by MCF1233 MuLV-specific CTL. Moreove r, in the Rauscher MuLV-induced cell line RMA the FMR peptide seems no t to be processed for recognition by CTL, which was illustrated by exp eriments with CTL elicited against this peptide. Altered TCR interacti on as well as lack of processing thus may explain the type specificity of MCF1233 MuLV-directed CTL.