The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product

Alex Y.C. Huang, Pamela H. Gulden, Amina S. Woods, Matthew C. Thomas, Caryn D. Tong, Wei Wang, Victor H. Engelhard, Gary Pasternack, Robert Cotter, Donald Hunt, Drew M. Pardoll, Elizabeth M. Jaffee

Research output: Contribution to journalArticlepeer-review

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-vital-induced tumors provides evidence for a unique class of shared immunodominant tumor associated antigens as targets for antitumor immunity.

Original languageEnglish (US)
Pages (from-to)9730-9735
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number18
DOIs
StatePublished - Sep 3 1996

Keywords

  • cytotoxic T lymphocytes
  • endogenous murine leukemia virus
  • major histocompatibility complex class I peptides
  • murine tumor antigens
  • tandem mass spectrometry

ASJC Scopus subject areas

  • General

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