INDUCTION OF CYTOTOXIC T-LYMPHOCYTES TO MURINE MAMMARY-TUMOR CELLS WITH A K-D-RESTRICTED IMMUNOGENIC PEPTIDE

A synthetic peptide E474 SFAVATTAL, derived from the sequence of mouse mammary tumor virus envelope protein, was previously shown to bind cl ass I MHC K-d. Immunization of BALB/c mice with E474 in 50% incomplete Freund's adjuvant (IFA) followed by in vitro stimulation of immune ce lls with E474-coated antigen-presenting cells resulted in peptide-spec ific cytotoxic T lymphocytes (CTL). Furthermore, anti-E474 CTL lysed m ammary tumor cell lines D2F2 and D2A1, derived from a spontaneous tumo r that arose in BALB/c pre-neoplastic hyperplastic alveolar nodule (HA N) D2 line. Expression of K-d by D2A1 and D2F2 cells was verified by f low cytometry, and lysis of D2 tumor cells was blocked by monoclonal a ntibody 31-3-4S, which interacted with the peptide-binding region of K -d, supporting the recognition of E474 in K-d by anti-E474 CTL. Immuni zation of BALB/c mice with E474 before D2F2 tumor challenge resulted i n reduced tumor growth. Therefore, E474 is naturally processed and pre sented by these tumor cells and can induce anti-tumor immunity. (C) 19 96 Wiley-Liss, Inc.