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Cytotoxic T Lymphocytes to An Unmutated Tumor Rejection Antigen P1A: Normal Development but Restrained Effector Function In Vivo

Unmutated tumor antigens are chosen as primary candidates for tumor vaccine because of their expression on multiple lineages of tumors. A critical issue is whether unmutated tumor antigens are expressed in normal cells, and if so, whether such expression imposes special restrictions on cytotoxic T l...

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Autores principales: Sarma, Supria, Guo, Yong, Guilloux, Yannik, Lee, Cheng, Bai, Xue-Feng, Liu, Yang
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192944/
https://www.ncbi.nlm.nih.gov/pubmed/10049945
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author Sarma, Supria
Guo, Yong
Guilloux, Yannik
Lee, Cheng
Bai, Xue-Feng
Liu, Yang
author_facet Sarma, Supria
Guo, Yong
Guilloux, Yannik
Lee, Cheng
Bai, Xue-Feng
Liu, Yang
author_sort Sarma, Supria
collection PubMed
description Unmutated tumor antigens are chosen as primary candidates for tumor vaccine because of their expression on multiple lineages of tumors. A critical issue is whether unmutated tumor antigens are expressed in normal cells, and if so, whether such expression imposes special restrictions on cytotoxic T lymphocyte (CTL) responses. In this study, we use a transgenic approach to study the development and effector function of T cells specific for P1A, a prototypical unmutated tumor antigen. We report here that although P1A is expressed at low levels in normal tissues, including lymphoid tissues, the P1A-specific transgenic T cells develop normally and remain highly responsive to the P1A antigen. The fact that transgenic expression of P1A antigen in the thymus induces T cell clonal deletion demonstrates that normal hematopoietic cells can process and present the P1A antigen and that P1A-specific T cells are susceptible to clonal deletion. By inference, P1A-specific T cells must have escaped clonal deletion due to low expression of P1A in the thymus. Interestingly, despite the fact that an overwhelming majority of T cells in the T cell receptor for antigen (TCR)–transgenic mice are specific for P1A, these mice are no more resistant to a P1A-expressing plasmocytoma than nontransgenic littermates. Moreover, when the same TCR-transgenic mice were challenged simultaneously with B7-1(+) and B7-1(−) tumors, only B7-1(+) tumors were rejected. Therefore, even though P1A can be a tumor rejection antigen, the effector function of P1A-specific CTL is restrained in vivo. These results have important implications for the strategy of tumor immunotherapy.
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spelling pubmed-21929442008-04-16 Cytotoxic T Lymphocytes to An Unmutated Tumor Rejection Antigen P1A: Normal Development but Restrained Effector Function In Vivo Sarma, Supria Guo, Yong Guilloux, Yannik Lee, Cheng Bai, Xue-Feng Liu, Yang J Exp Med Articles Unmutated tumor antigens are chosen as primary candidates for tumor vaccine because of their expression on multiple lineages of tumors. A critical issue is whether unmutated tumor antigens are expressed in normal cells, and if so, whether such expression imposes special restrictions on cytotoxic T lymphocyte (CTL) responses. In this study, we use a transgenic approach to study the development and effector function of T cells specific for P1A, a prototypical unmutated tumor antigen. We report here that although P1A is expressed at low levels in normal tissues, including lymphoid tissues, the P1A-specific transgenic T cells develop normally and remain highly responsive to the P1A antigen. The fact that transgenic expression of P1A antigen in the thymus induces T cell clonal deletion demonstrates that normal hematopoietic cells can process and present the P1A antigen and that P1A-specific T cells are susceptible to clonal deletion. By inference, P1A-specific T cells must have escaped clonal deletion due to low expression of P1A in the thymus. Interestingly, despite the fact that an overwhelming majority of T cells in the T cell receptor for antigen (TCR)–transgenic mice are specific for P1A, these mice are no more resistant to a P1A-expressing plasmocytoma than nontransgenic littermates. Moreover, when the same TCR-transgenic mice were challenged simultaneously with B7-1(+) and B7-1(−) tumors, only B7-1(+) tumors were rejected. Therefore, even though P1A can be a tumor rejection antigen, the effector function of P1A-specific CTL is restrained in vivo. These results have important implications for the strategy of tumor immunotherapy. The Rockefeller University Press 1999-03-01 /pmc/articles/PMC2192944/ /pubmed/10049945 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Sarma, Supria
Guo, Yong
Guilloux, Yannik
Lee, Cheng
Bai, Xue-Feng
Liu, Yang
Cytotoxic T Lymphocytes to An Unmutated Tumor Rejection Antigen P1A: Normal Development but Restrained Effector Function In Vivo
title Cytotoxic T Lymphocytes to An Unmutated Tumor Rejection Antigen P1A: Normal Development but Restrained Effector Function In Vivo
title_full Cytotoxic T Lymphocytes to An Unmutated Tumor Rejection Antigen P1A: Normal Development but Restrained Effector Function In Vivo
title_fullStr Cytotoxic T Lymphocytes to An Unmutated Tumor Rejection Antigen P1A: Normal Development but Restrained Effector Function In Vivo
title_full_unstemmed Cytotoxic T Lymphocytes to An Unmutated Tumor Rejection Antigen P1A: Normal Development but Restrained Effector Function In Vivo
title_short Cytotoxic T Lymphocytes to An Unmutated Tumor Rejection Antigen P1A: Normal Development but Restrained Effector Function In Vivo
title_sort cytotoxic t lymphocytes to an unmutated tumor rejection antigen p1a: normal development but restrained effector function in vivo
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192944/
https://www.ncbi.nlm.nih.gov/pubmed/10049945
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