Irrelevance of the mutated p53 gene product to tumor rejection antigen in 3-methylcholanthrene-induced fibrosarcomas.

: The relevance of mutated p53 to in vivo rejection of MC-induced fibrosarcomas and/or in vitro CTL activity against these tumors was investigated. p53 gene was found to be altered in nine MC-induced fibrosarcomas of BALB/c origin. The mutated p53 cDNA derived from several MC-induced fibrosarcomas was transduced into CMS8 which lacks p53 expression. Immunization of mice with these mutated p53 transfectants failed to protect them from original MC-induced fibrosarcomas from which mutated p53 genes were derived. CTL lines specific for these MC-induced fibrosarcomas destroyed the original MC-induced fibrosarcomas, but not CMS8 transduced with mutated p53 genes derived from the same lines. A series of 9mer peptides consisting of mutated amino acid residues of p53 of Meth A, CMS17 and CMS9 were prepared, and target P1HTR cells were pulsed with them. None of CTLs for these fibrosarcomas were reactive with P1HTR pulsed with these peptides. In conclusion, peptides derived from mutated p53 genes may serve as target antigens for CD8(+) MHC class I restricted CTL as reported, but may often not contribute as target antigens to the rejection of MC-induced fibrosarcomas.