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An immunodominant MHC class II-restricted tumor antigen is conformation dependent and binds to the endoplasmic reticulum chaperone, calreticulin

An immunodominant MHC class II-restricted tumor antigen is conformation dependent and binds to the endoplasmic reticulum chaperone, calreticulin
An immunodominant MHC class II-restricted tumor antigen is conformation dependent and binds to the endoplasmic reticulum chaperone, calreticulin
There is accumulating evidence that CD4+ T cell responses are important in antitumor immunity. Accordingly, we generated CD4+ T cells against the murine CT26 colon cancer. Three of three independent CT26-specific CD4+ hybridomas were found to recognize the high m.w. precursor of the env gene product gp90. The CD4+ response was completely tumor specific in that the same glycoprotein expressed by other tumors was not recognized by the CT26-specific hybridomas. The recognition of gp90 by the hybridomas was strictly dependent on the conformation of gp90. Different procedures that disrupted the conformation of the glycoprotein, such as disulfide bond reduction and thermal denaturation, completely abrogated recognition of gp90 by all three hybridomas. In CT26 cells, but not in other tumor cells tested, a large proportion of gp90 was retained in the endoplasmic reticulum, mostly bound to the endoplasmic reticulum chaperone, calreticulin. Although calreticulin was not essential for the stimulation of the gp90-specific hybridomas, most of the antigenic form of gp90 was bound to it. The antigenicity of gp90 correlated well with calreticulin binding, reflecting the fact that specificity of binding of calreticulin to its substrate required posttranslational modifications that were also necessary for the generation of this tumor-specific CD4+ epitope.
0022-1767
147-155
Golgher, Denise
9f810d0e-e5f6-48be-84a3-2631ea385816
Korangy, Firouzeh
71904c44-e3ab-4998-955a-60aac1ea4362
Gao, Bin
763f5d11-2809-4cea-a518-7f55037bceba
Gorski, Kevin
1b71ac9e-9ae0-44ca-96ba-2140e7a1ebcd
Jaffee, Elizabeth
3288b603-7aa1-4ecd-90ec-6328de88a9e0
Edidin, Michael
82c5377f-3b5f-420f-892f-96326f815ad8
Pardoll, Drew M.
edbdb758-cb18-4421-aaaa-8f7059e75c3b
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Golgher, Denise
9f810d0e-e5f6-48be-84a3-2631ea385816
Korangy, Firouzeh
71904c44-e3ab-4998-955a-60aac1ea4362
Gao, Bin
763f5d11-2809-4cea-a518-7f55037bceba
Gorski, Kevin
1b71ac9e-9ae0-44ca-96ba-2140e7a1ebcd
Jaffee, Elizabeth
3288b603-7aa1-4ecd-90ec-6328de88a9e0
Edidin, Michael
82c5377f-3b5f-420f-892f-96326f815ad8
Pardoll, Drew M.
edbdb758-cb18-4421-aaaa-8f7059e75c3b
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e

Golgher, Denise, Korangy, Firouzeh, Gao, Bin, Gorski, Kevin, Jaffee, Elizabeth, Edidin, Michael, Pardoll, Drew M. and Elliott, Tim (2001) An immunodominant MHC class II-restricted tumor antigen is conformation dependent and binds to the endoplasmic reticulum chaperone, calreticulin. Journal of Immunology, 167 (1), 147-155.

Record type: Article

Abstract

There is accumulating evidence that CD4+ T cell responses are important in antitumor immunity. Accordingly, we generated CD4+ T cells against the murine CT26 colon cancer. Three of three independent CT26-specific CD4+ hybridomas were found to recognize the high m.w. precursor of the env gene product gp90. The CD4+ response was completely tumor specific in that the same glycoprotein expressed by other tumors was not recognized by the CT26-specific hybridomas. The recognition of gp90 by the hybridomas was strictly dependent on the conformation of gp90. Different procedures that disrupted the conformation of the glycoprotein, such as disulfide bond reduction and thermal denaturation, completely abrogated recognition of gp90 by all three hybridomas. In CT26 cells, but not in other tumor cells tested, a large proportion of gp90 was retained in the endoplasmic reticulum, mostly bound to the endoplasmic reticulum chaperone, calreticulin. Although calreticulin was not essential for the stimulation of the gp90-specific hybridomas, most of the antigenic form of gp90 was bound to it. The antigenicity of gp90 correlated well with calreticulin binding, reflecting the fact that specificity of binding of calreticulin to its substrate required posttranslational modifications that were also necessary for the generation of this tumor-specific CD4+ epitope.

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Published date: 2001

Identifiers

Local EPrints ID: 26327
URI: http://eprints.soton.ac.uk/id/eprint/26327
ISSN: 0022-1767
PURE UUID: ba5e0b70-89a7-4a9b-90ed-42b711fefde0
ORCID for Tim Elliott: ORCID iD orcid.org/0000-0003-1097-0222

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Date deposited: 24 Apr 2006
Last modified: 23 Jul 2022 01:48

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Contributors

Author: Denise Golgher
Author: Firouzeh Korangy
Author: Bin Gao
Author: Kevin Gorski
Author: Elizabeth Jaffee
Author: Michael Edidin
Author: Drew M. Pardoll
Author: Tim Elliott ORCID iD

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