1. The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product.
- Author
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Huang AY, Gulden PH, Woods AS, Thomas MC, Tong CD, Wang W, Engelhard VH, Pasternack G, Cotter R, Hunt D, Pardoll DM, and Jaffee EM
- Subjects
- Animals, Antigens, Neoplasm genetics, Antigens, Viral genetics, Base Sequence, Cell Line, Chromatography, High Pressure Liquid, Colorectal Neoplasms virology, Granulocyte-Macrophage Colony-Stimulating Factor metabolism, Immunodominant Epitopes immunology, Leukemia Virus, Murine genetics, Leukemia Virus, Murine metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred DBA, Molecular Sequence Data, Polymerase Chain Reaction, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Cytotoxic metabolism, Antigens, Neoplasm immunology, Antigens, Viral immunology, Colorectal Neoplasms immunology, Histocompatibility Antigens Class I immunology, Leukemia Virus, Murine immunology
- Abstract
Tumors express peptide antigens capable of being recognized by tumor-specific cytotoxic T lymphocytes (CTL). Immunization of mice with a carcinogen-induced colorectal tumor, CT26, engineered to secrete granulocyte/macrophage colony-stimulating factor, routinely generated both short-term and long-term CTL lines that not only lysed the parental tumor in vitro, but also cured mice of established tumor following adoptive transfer in vivo. When either short-term or long-term CTL lines were used to screen peptides isolated from CT26, one reverse-phase high performance liquid chromatography peptide fraction consistently sensitized a surrogate target for specific lysis. The bioactivity remained localized within one fraction following multiple purification procedures, indicating that virtually all of the CT26-specific CTL recognized a single peptide. This result contrasts with other tumor systems, where multiple bioactive peptide fractions have been detected. The bioactive peptide was identified as a nonmutated nonamer derived from the envelope protein (gp70) of an endogenous ecotropic murine leukemia provirus. Adoptive transfer with CTL lines specific for this antigen demonstrated that this epitope represents a potent tumor rejection antigen. The selective expression of this antigen in multiple non-viral-induced tumors provides evidence for a unique class of shared immunodominant tumor associated antigens as targets for antitumor immunity.
- Published
- 1996
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