First Author | Akilesh S | Year | 2001 |
Journal | J Immunol | Volume | 167 |
Issue | 9 | Pages | 5143-9 |
PubMed ID | 11673526 | Mgi Jnum | J:72671 |
Mgi Id | MGI:2153384 | Doi | 10.4049/jimmunol.167.9.5143 |
Citation | Akilesh S, et al. (2001) Efficient chromosomal mapping of a methylcholanthrene- induced tumor antigen by ctl immunoselection. J Immunol 167(9):5143-9 |
abstractText | 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. |