title: Efficient chromosomal mapping of a methylcholanthrene-induced tumor antigen by CTL immunoselection.
abstract: It has been difficult to genetically map the genes encoding tumor Ags because they arise as a consequence of somatic mutational events. CTL-mediated immunoselection can impose potent immunoselective pressure against tumor cells, resulting in the survival of rare tumor Ag-loss variants. We subjected a heterozygous 3-methylcholanthrene-induced murine sarcoma cell line to CTL immunoselection, selecting for the loss of a tumor-specific Ag, recognized antigen from MCA-induced tumor 1 (Ram1). Several variants eluded CTL recognition by genetic loss of the hemizygously expressed tumor-specific Ag epitope. A frequently observed genetic escape mechanism was spontaneous mitotic recombination resulting in loss of heterozygosity on chromosome 4. Higher density genetic analyses along with functional confirmation with an independently produced chromosome 4 loss of heterozygosity variant positioned the Ram1 locus to a distal 7.1 cM interval on chromosome 4. This region of the mouse genome is rich in tumor-modifier genes and this positioning of Ram1 may thus provide insight into the genetic basis of 3-methycholanthrene-induced tumor Ags.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: S
authors.initials: S
authors.lastname: Akilesh
authors.forename: M E
authors.initials: ME
authors.lastname: Dudley
authors.forename: P A
authors.initials: PA
authors.lastname: Eden
authors.forename: D C
authors.initials: DC
authors.lastname: Roopenian
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D005805:Genes, MHC Class I; D019656:Loss of Heterozygosity; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D008748:Methylcholanthrene