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Publication : Efficient chromosomal mapping of a methylcholanthrene-induced tumor antigen by CTL immunoselection.

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.
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