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-alpha (TNF-alpha) release assays concurred with the in vivo rejection tests. The strongest response in the TNF-alpha 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-alpha 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-alpha 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.
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Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Petersson
M
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Ciupitu
A M
AM
Wen
T
T
Klein
G
G
Kiessling
R
R
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D008748:Methylcholanthrene