The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product.
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.
Huang
A Y
AY
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Gulden
P H
PH
Woods
A S
AS
Thomas
M C
MC
Tong
C D
CD
Wang
W
W
Engelhard
V H
VH
Pasternack
G
G
Cotter
R
R
Hunt
D
D
Pardoll
D M
DM
Jaffee
E M
EM
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000821:virology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor