THE MOUSE MAMMARY-TUMOR VIRUS ENV GENE IS THE SOURCE OF A CD8(-CELL-STIMULATING PEPTIDE PRESENTED BY A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE IN A MURINE THYMOMA() T)

CD8(+) cytotoxic T cells recognize their targets by the presence of un ique peptide bound to a major histocompatibility complex (ME-IC) class I molecules on the cell surface. The MHC molecules normally display t housands of distinct peptides, making it difficult to identify individ ual antigenic peptides, their protein precursors, and their relative i mportance in the T-cell response. sere we used the EL-4 tumor-specific lacZ-inducible KZ30.6 T cell as a probe for detecting the peptide/MHC ligand that was generated in cells transfected with an EL-4 cDNA libr ary, These expression screens allowed identification of a mouse mammar y tumor virus (MMTV) transcript as the source of the antigenic peptide presented by the K-b MHC molecule. The antigenic activity was encoded within the MMTV env gene and was defined by the octapeptide ANYDFICV (AFV8). Synthetic AFV8 stimulated KZ30.6 T cells at picomolar concentr ations and coeluted with one of two active peptides in HPLC-fractionat ed extracts of EL-4 cells. The AFV8/K-b complex was also recognized by two other EL-4-specific T cells. The results illustrate a novel strat egy for identifying T-cell-stimulating antigens and suggest that the M MTV env gene and its naturally processed AFV8 peptide product can serv e as a model for study of antigen processing and tumor immunotherapy.