Methylcholanthrene-induced Mouse Sarcomas Express Individually Distinct Major Histocompatibility Complex Class I-associated Peptides Recognized by Specific CD8+ T-Cell Lines

Mouse sarcomas induced by methylcholanthrene (MC) are immunologically distinct even if they are induced in the same strain of mice. T-cell lines were derived from mice immunized against a series of syngeneic MC sarcomas on B6 background, known to carry unique tumor-specific transplantation antigens. Tumor necrosis factor-a (TNF-a) release assays concurred with the in vivo rejection tests. The strongest response in the TNF-a release was always obtained with the corresponding tumor, with very limited cross-reactivity against five other MC tumors or two virally induced B6 lymphomas. The specific TNF-a release from the anti-MC tumor CTL lines was mainly mediated by CD8+ cells. T-cell lines from intact and CD4-/- mice gave a similarly specific pattern. In contrast, T-cell lines derived from CD8-/- mice cross-reacted with several other MC-induced tumors. Peptides eluted from MC sarcomas under mild acid conditions were fractionated by reverse-phase high performance liquid chromatography and tested for their ability to sensitize the processing-and presentation-defective mutant RMA-S line. Only one high performance liquid chromatographic fraction from each of the three different tumor-derived peptide eluates capacitated RMA-S to induce TNF-a release and sensitized the cell to the cytotoxic effect of the corresponding tumor-specific T-cell line. A different Kb-restricted peptide fraction was active for each of the three MC sarcomas tested, indicating that they all expressed individually distinct peptide epitopes.