Related Experiment Videos
Mutated mitogen-activated protein kinase: a tumor rejection antigen of mouse sarcoma
12nd Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514, Japan.
Abstract:
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.
Insights
Researchers identified a mutated mitogen-activated protein kinase (ERK2) as a tumor rejection antigen in mouse sarcomas. Vaccination with a peptide from this mutated ERK2 provided resistance against tumor challenge, suggesting its essential role in cancer.
Area of Science:
- Tumor Immunology
- Molecular Biology
- Cancer Research
Background:
- The molecular basis of polymorphic tumor rejection antigens in chemically induced sarcomas has remained elusive for over 40 years.
- These antigens are crucial for understanding tumor immunology and developing cancer therapies.