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 J. Cotter, Donald Hunt, Andrew Mark Pardoll, Elizabeth Jaffee

Research output: Contribution to journalArticle

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

Fingerprint

Histocompatibility Antigens Class I
Major Histocompatibility Complex
Cytotoxic T-Lymphocytes
Colon
Peptides
Genes
Neoplasms
Adoptive Transfer
Neoplasm Antigens
Antigens
Proviruses
Immunodominant Epitopes
Reverse-Phase Chromatography
Granulocyte-Macrophage Colony-Stimulating Factor
Carcinogens
Epitopes
Colorectal Neoplasms
Immunity
Immunization
Leukemia

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product. / Huang, Alex Y C; Gulden, Pamela H.; Woods, Amina S.; Thomas, Matthew C.; Tong, Caryn D.; Wang, Wei; Engelhard, Victor H.; Pasternack, Gary; Cotter, Robert J.; Hunt, Donald; Pardoll, Andrew Mark; Jaffee, Elizabeth.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 18, 03.09.1996, p. 9730-9735.

Research output: Contribution to journalArticle

Huang, Alex Y C ; Gulden, Pamela H. ; Woods, Amina S. ; Thomas, Matthew C. ; Tong, Caryn D. ; Wang, Wei ; Engelhard, Victor H. ; Pasternack, Gary ; Cotter, Robert J. ; Hunt, Donald ; Pardoll, Andrew Mark ; Jaffee, Elizabeth. / The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 18. pp. 9730-9735.
@article{f80b2800b3c5433cb4b7253511e6d5fb,
title = "The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product",
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.",
keywords = "cytotoxic T lymphocytes, endogenous murine leukemia virus, major histocompatibility complex class I peptides, murine tumor antigens, tandem mass spectrometry",
author = "Huang, {Alex Y C} and Gulden, {Pamela H.} and Woods, {Amina S.} and Thomas, {Matthew C.} and Tong, {Caryn D.} and Wei Wang and Engelhard, {Victor H.} and Gary Pasternack and Cotter, {Robert J.} and Donald Hunt and Pardoll, {Andrew Mark} and Elizabeth Jaffee",
year = "1996",
month = "9",
day = "3",
doi = "10.1073/pnas.93.18.9730",
language = "English (US)",
volume = "93",
pages = "9730--9735",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "18",

}

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 J.

AU - Hunt, Donald

AU - Pardoll, Andrew Mark

AU - Jaffee, Elizabeth

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

UR - http://www.scopus.com/inward/record.url?scp=9544221745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9544221745&partnerID=8YFLogxK

U2 - 10.1073/pnas.93.18.9730

DO - 10.1073/pnas.93.18.9730

M3 - Article

C2 - 8790399

AN - SCOPUS:9544221745

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

SN - 0027-8424

IS - 18

ER -