title: Tumour cell variants with increased immunogenicity obtained by mutagen treatment.
abstract: By treating mouse tumour cells in vitro with mutagens it is possible to obtain at high frequency variants that are rejected by normal syngeneic mice. Such variants have been designated 'tum-' to distinguish them from the original tumorigenic (tum+) cell lines. Most tum- variants appear to express new, individual antigens that can be defined in vivo by cross-protection experiments or in vitro by cytolytic T lymphocytes. The failure of tum- variants to form progressive tumours is apparently the result of an immune rejection response. Mice that have rejected a tum- variant clone are often protected against a subsequent challenge with the original tum+ cells. This was even demonstrated for two spontaneous mouse tumours for which no immunogenicity could be demonstrated otherwise. An analysis of 21 variants derived from mastocytoma P815 with cytolytic T lymphocyte populations showed that the repertoire of tum- antigens probably exceeds 50 specificities. No two variants have been found to express the same new antigen. Variant-specific long-term cytolytic T lymphocyte clones were isolated and used for the immunoselection of secondary antigen-loss variants that could then be analysed for the presence of previously undefined residual variant antigenic determinants. Somatic cell hybrids were prepared between different P815 tum- variants or between tum- variants and the original P815 cells. An analysis of the hybrids with variant-specific cytolytic T lymphocyte clones showed that the expression of tum- antigens was dominant. The intriguing paradox of the high frequency of tum- variants in populations of mutagen-treated tumour cells may require new genetic and immunological approaches before being understood.
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002460:Cell Line; D014644:Genetic Variation; D006084:Graft Rejection; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D051379:Mice; D009153:Mutagens; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D009153:Mutagens; D008769:Methylnitronitrosoguanidine