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Publication : Mutated mitogen-activated protein kinase: a tumor rejection antigen of mouse sarcoma.

First Author  Ikeda H Year  1997
Journal  Proc Natl Acad Sci U S A Volume  94
Issue  12 Pages  6375-9
PubMed ID  9177225 Mgi Jnum  J:40973
Mgi Id  MGI:892692 Doi  10.1073/pnas.94.12.6375
Citation  Ikeda H, et al. (1997) Mutated mitogen-activated protein kinase: a tumor rejection antigen of mouse sarcoma. Proc Natl Acad Sci U S A 94(12):6375-9
abstractText  The molecular basis of the polymorphic tumor rejection antigens of chemically induced sarcomas of inbred mice remains a mystery, despite the discovery of these antigens over 40 years ago and their critical importance to the foundation of tumor immunology. In an analysis of a panel of BALB/c 3-methylcholanthrene-induced tumors, we identified one tumor, CMS5, that elicited a strong cytotoxic T cell response with exquisite specificity for CMS5. A stable cloned line of T cells with this specificity (C18) was used to screen a CMS5 cDNA expression library. The gene encoding the C18-defined antigen was identified as a mutated form of a mouse mitogen-activated protein kinase, ERK2, and a peptide incorporating the resulting amino acid substitution (lysine to glutamine) was efficiently recognized by C18. Vaccination with this peptide elicited specific resistance to CMS5 challenge. Extensive efforts to isolate antigen-loss variants of CMS5 were unsuccessful, suggesting that the mutated mitogen-activated protein kinase is essential for maintenance of the malignant phenotype.
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