Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies
Epstein-Barr virus (EBV) is a gamma herpesvirus that causes a life-long latent infection in human hosts. The latent gene products LMP1, LMP2A and EBNA1 are expressed by EBV-associated tumors and peptide epitopes derived from these can be targeted by CD8 Cytotoxic T-Lymphocyte (CTL) lines. Whilst CTL...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/85918 https://orcid.org/0000-0002-5687-6154 |
| _version_ | 1826197443325198336 |
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| author | Sim, Adrian Chong Nyi Too, Chien Tei Oo, Min Zin Lai, Junyun Eio, Michelle Yating Song, Zhenying Srinivasan, Nalini Tan, Diane Ai Lin Pang, Shyue Wei Gan, Shu Uin Lee, Kok Onn Loh, Thomas Kwok Seng Chen, Jianzhu Chan, Soh Ha MacAry, Paul Anthony |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Sim, Adrian Chong Nyi Too, Chien Tei Oo, Min Zin Lai, Junyun Eio, Michelle Yating Song, Zhenying Srinivasan, Nalini Tan, Diane Ai Lin Pang, Shyue Wei Gan, Shu Uin Lee, Kok Onn Loh, Thomas Kwok Seng Chen, Jianzhu Chan, Soh Ha MacAry, Paul Anthony |
| author_sort | Sim, Adrian Chong Nyi |
| collection | MIT |
| description | Epstein-Barr virus (EBV) is a gamma herpesvirus that causes a life-long latent infection in human hosts. The latent gene products LMP1, LMP2A and EBNA1 are expressed by EBV-associated tumors and peptide epitopes derived from these can be targeted by CD8 Cytotoxic T-Lymphocyte (CTL) lines. Whilst CTL-based methodologies can be utilized to infer the presence of specific latent epitopes, they do not allow a direct visualization or quantitation of these epitopes. Here, we describe the characterization of three TCR-like monoclonal antibodies (mAbs) targeting the latent epitopes LMP1[subscript 125–133], LMP2A[subscript 426–434] or EBNA1[subscript 562–570] in association with HLA-A0201. These are employed to map the expression hierarchy of endogenously generated EBV epitopes. The dominance of EBNA1[subscript 562–570] in association with HLA-A0201 was consistently observed in cell lines and EBV-associated tumor biopsies. These data highlight the discordance between MHC-epitope density and frequencies of associated CTL with implications for cell-based immunotherapies and/or vaccines for EBV-associated disease. |
| first_indexed | 2024-09-23T10:48:05Z |
| format | Article |
| id | mit-1721.1/85918 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:48:05Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/859182022-09-27T15:04:21Z Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies Sim, Adrian Chong Nyi Too, Chien Tei Oo, Min Zin Lai, Junyun Eio, Michelle Yating Song, Zhenying Srinivasan, Nalini Tan, Diane Ai Lin Pang, Shyue Wei Gan, Shu Uin Lee, Kok Onn Loh, Thomas Kwok Seng Chen, Jianzhu Chan, Soh Ha MacAry, Paul Anthony Massachusetts Institute of Technology. Department of Biology Chen, Jianzhu Epstein-Barr virus (EBV) is a gamma herpesvirus that causes a life-long latent infection in human hosts. The latent gene products LMP1, LMP2A and EBNA1 are expressed by EBV-associated tumors and peptide epitopes derived from these can be targeted by CD8 Cytotoxic T-Lymphocyte (CTL) lines. Whilst CTL-based methodologies can be utilized to infer the presence of specific latent epitopes, they do not allow a direct visualization or quantitation of these epitopes. Here, we describe the characterization of three TCR-like monoclonal antibodies (mAbs) targeting the latent epitopes LMP1[subscript 125–133], LMP2A[subscript 426–434] or EBNA1[subscript 562–570] in association with HLA-A0201. These are employed to map the expression hierarchy of endogenously generated EBV epitopes. The dominance of EBNA1[subscript 562–570] in association with HLA-A0201 was consistently observed in cell lines and EBV-associated tumor biopsies. These data highlight the discordance between MHC-epitope density and frequencies of associated CTL with implications for cell-based immunotherapies and/or vaccines for EBV-associated disease. 2014-03-24T20:02:51Z 2014-03-24T20:02:51Z 2013-11 2013-08 Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/85918 Sim, Adrian Chong Nyi, Chien Tei Too, Min Zin Oo, Junyun Lai, Michelle Yating Eio, Zhenying Song, Nalini Srinivasan, et al. “Defining the Expression Hierarchy of Latent T-Cell Epitopes in Epstein-Barr Virus Infection with TCR-Like Antibodies.” Sci. Rep. 3 (November 18, 2013). https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1038/srep03232 Scientific Reports Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Nature Publishing Group Nature Publishing Group |
| spellingShingle | Sim, Adrian Chong Nyi Too, Chien Tei Oo, Min Zin Lai, Junyun Eio, Michelle Yating Song, Zhenying Srinivasan, Nalini Tan, Diane Ai Lin Pang, Shyue Wei Gan, Shu Uin Lee, Kok Onn Loh, Thomas Kwok Seng Chen, Jianzhu Chan, Soh Ha MacAry, Paul Anthony Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies |
| title | Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies |
| title_full | Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies |
| title_fullStr | Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies |
| title_full_unstemmed | Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies |
| title_short | Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies |
| title_sort | defining the expression hierarchy of latent t cell epitopes in epstein barr virus infection with tcr like antibodies |
| url | http://hdl.handle.net/1721.1/85918 https://orcid.org/0000-0002-5687-6154 |
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