Mutated mitogen-activated protein kinase: a tumor rejection antigen of mouse sarcoma.
Proc Natl Acad Sci U S A
; 94(12): 6375-9, 1997 Jun 10.
Article
en En
| MEDLINE
| ID: mdl-9177225
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sarcoma Experimental
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Linfocitos T Citotóxicos
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Proteínas Quinasas Dependientes de Calcio-Calmodulina
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Citotoxicidad Inmunológica
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Rechazo de Injerto
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Trasplante de Neoplasias
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
1997
Tipo del documento:
Article
País de afiliación:
Japón