Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity
We have generated, via somatic cell nuclear transfer, two independent lines of transnuclear (TN) mice, using as nuclear donors CD8 T cells, sorted by tetramer staining, that recognize the endogenous melanoma antigen TRP1. These two lines of nominally identical specificity differ greatly in their aff...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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American Association for Cancer Research (AACR)
2018
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| Online Access: | http://hdl.handle.net/1721.1/116615 |
| _version_ | 1826190944438845440 |
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| author | Dougan, S. K. Dougan, M. Turner, J. A. Ogata, S. Cho, H.-I. Jaenisch, R. Celis, E. Ploegh, H. L. Kim, Jun |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Dougan, S. K. Dougan, M. Turner, J. A. Ogata, S. Cho, H.-I. Jaenisch, R. Celis, E. Ploegh, H. L. Kim, Jun |
| author_sort | Dougan, S. K. |
| collection | MIT |
| description | We have generated, via somatic cell nuclear transfer, two independent lines of transnuclear (TN) mice, using as nuclear donors CD8 T cells, sorted by tetramer staining, that recognize the endogenous melanoma antigen TRP1. These two lines of nominally identical specificity differ greatly in their affinity for antigen (TRP1(high) or TRP1(low)) as inferred from tetramer dissociation and peptide responsiveness. Ex vivo-activated CD8 T cells from either TRP1(high) or TRP1(low) mice show cytolytic activity in 3D tissue culture and in vivo, and slow the progression of subcutaneous B16 melanoma. Although naïve TRP1(low) CD8 T cells do not affect tumor growth, upon activation these cells function indistinguishably from TRP1(high) cells in vivo, limiting tumor cell growth and increasing mouse survival. The anti-tumor effect of both TRP1(high) and TRP1(low) CD8 T cells is enhanced in RAG-deficient hosts. However, tumor outgrowth eventually occurs, likely due to T cell exhaustion. The TRP1 TN mice are an excellent model for examining the functional attributes of T cells conferred by TCR affinity, and they may serve as a platform for screening immunomodulatory cancer therapies. |
| first_indexed | 2024-09-23T08:47:42Z |
| format | Article |
| id | mit-1721.1/116615 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T08:47:42Z |
| publishDate | 2018 |
| publisher | American Association for Cancer Research (AACR) |
| record_format | dspace |
| spelling | mit-1721.1/1166152022-09-30T11:19:37Z Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity Dougan, S. K. Dougan, M. Turner, J. A. Ogata, S. Cho, H.-I. Jaenisch, R. Celis, E. Ploegh, H. L. Kim, Jun Massachusetts Institute of Technology. Department of Biology Kim, Jun We have generated, via somatic cell nuclear transfer, two independent lines of transnuclear (TN) mice, using as nuclear donors CD8 T cells, sorted by tetramer staining, that recognize the endogenous melanoma antigen TRP1. These two lines of nominally identical specificity differ greatly in their affinity for antigen (TRP1(high) or TRP1(low)) as inferred from tetramer dissociation and peptide responsiveness. Ex vivo-activated CD8 T cells from either TRP1(high) or TRP1(low) mice show cytolytic activity in 3D tissue culture and in vivo, and slow the progression of subcutaneous B16 melanoma. Although naïve TRP1(low) CD8 T cells do not affect tumor growth, upon activation these cells function indistinguishably from TRP1(high) cells in vivo, limiting tumor cell growth and increasing mouse survival. The anti-tumor effect of both TRP1(high) and TRP1(low) CD8 T cells is enhanced in RAG-deficient hosts. However, tumor outgrowth eventually occurs, likely due to T cell exhaustion. The TRP1 TN mice are an excellent model for examining the functional attributes of T cells conferred by TCR affinity, and they may serve as a platform for screening immunomodulatory cancer therapies. 2018-06-26T14:39:36Z 2018-06-26T14:39:36Z 2013-07 2013-07 2018-06-26T14:10:35Z Article http://purl.org/eprint/type/JournalArticle 2326-6066 2326-6074 http://hdl.handle.net/1721.1/116615 Dougan, S. K. et al. “Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity.” Cancer Immunology Research 1, 2 (July 2013): 99–111 © 2013 American Association for Cancer Research (AACR) http://dx.doi.org/10.1158/2326-6066.CIR-13-0047 Cancer Immunology Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research (AACR) PMC |
| spellingShingle | Dougan, S. K. Dougan, M. Turner, J. A. Ogata, S. Cho, H.-I. Jaenisch, R. Celis, E. Ploegh, H. L. Kim, Jun Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity |
| title | Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity |
| title_full | Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity |
| title_fullStr | Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity |
| title_full_unstemmed | Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity |
| title_short | Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity |
| title_sort | transnuclear trp1 specific cd8 t cells with high or low affinity tcrs show equivalent antitumor activity |
| url | http://hdl.handle.net/1721.1/116615 |
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