RECOGNITION OF ENDOGENOUS ECOTROPIC MURINE LEUKEMIA VIRUSES BY ANTI-AKR GROSS VIRUS CYTOTOXIC T-LYMPHOCYTES (CTL) - EPITOPE VARIATION IN A CTL-RESISTANT VIRUS/

AKR/Gross virus-specific cytotoxic T lymphocytes (CTL) from C57BL/6 (B 6) mice are H-2K(b)-restricted and recognize epitopes encoded by the p rototype endogenous ecotropic murine leukaemia virus (Emv) AKR623, Fou r CTL epitopes have been identified by the use of synthetic peptides c orresponding to AKR623-encoded amino acid sequences. Here we present b oth functional and nucleotide sequence data indicating that three clos ely related Emv share all of these CTL epitopes. We also found that on e other murine leukaemia virus (MuLV) was not susceptible to lysis by these CTL. This is the ecotropic component of the LP-BM5 virus complex that causes murine AIDS. Nucleotide sequencing revealed that three of the four epitopes, including the immunodominant peptide, are altered in this virus. The other epitope was unchanged. These data implied tha t the inability of anti-AKR/Gross virus CTL to lyse cells infected wit h the LP-BM5 ecotropic (BM5eco) MuLV was due to the functional loss of three of the four CTL epitopes. Using recombinant vaccinia and Sindbi s virus vectors, we have shown that the BM5eco-encoded form of the imm unodominant epitope, which differs only by an arginine for lysine subs titution at the N-terminal residue, fails to induce a CTL response in B6 mice. Immunization with BM5eco-infected cells also failed to induce MuLV-specific CTL. In light of the long in vivo passage history of th e LP-BM5 complex in B6 mice, our results are consistent with a contrib ution of CTL-mediated immune selection to the evolution of the BM5eco MuLV.