TY - JOUR
T1 - The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product
AU - Huang, Alex Y.C.
AU - Gulden, Pamela H.
AU - Woods, Amina S.
AU - Thomas, Matthew C.
AU - Tong, Caryn D.
AU - Wang, Wei
AU - Engelhard, Victor H.
AU - Pasternack, Gary
AU - Cotter, Robert
AU - Hunt, Donald
AU - Pardoll, Drew M.
AU - Jaffee, Elizabeth M.
PY - 1996/9/3
Y1 - 1996/9/3
N2 - 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.
AB - 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.
KW - cytotoxic T lymphocytes
KW - endogenous murine leukemia virus
KW - major histocompatibility complex class I peptides
KW - murine tumor antigens
KW - tandem mass spectrometry
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U2 - 10.1073/pnas.93.18.9730
DO - 10.1073/pnas.93.18.9730
M3 - Article
C2 - 8790399
AN - SCOPUS:9544221745
SN - 0027-8424
VL - 93
SP - 9730
EP - 9735
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 18
ER -