Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use.
T-cell therapy of chronic hepatitis B is a novel approach to restore antiviral T-cell immunity and cure the infection. We aimed at identifying T-cell receptors (TCR) with high functional avidity that have the potential to be used for adoptive T-cell therapy. To this end, we cloned HLA-A*02-restricte...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182936&type=printable |
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| author | Karin Wisskirchen Kai Metzger Sophia Schreiber Theresa Asen Luise Weigand Christina Dargel Klaus Witter Elisa Kieback Martin F Sprinzl Wolfgang Uckert Matthias Schiemann Dirk H Busch Angela M Krackhardt Ulrike Protzer Ulrike Protzer |
| author_facet | Karin Wisskirchen Kai Metzger Sophia Schreiber Theresa Asen Luise Weigand Christina Dargel Klaus Witter Elisa Kieback Martin F Sprinzl Wolfgang Uckert Matthias Schiemann Dirk H Busch Angela M Krackhardt Ulrike Protzer Ulrike Protzer |
| author_sort | Karin Wisskirchen |
| collection | DOAJ |
| description | T-cell therapy of chronic hepatitis B is a novel approach to restore antiviral T-cell immunity and cure the infection. We aimed at identifying T-cell receptors (TCR) with high functional avidity that have the potential to be used for adoptive T-cell therapy. To this end, we cloned HLA-A*02-restricted, hepatitis B virus (HBV)-specific T cells from patients with acute or resolved HBV infection. We isolated 11 envelope- or core-specific TCRs and evaluated them in comprehensive functional analyses. T cells were genetically modified by retroviral transduction to express HBV-specific TCRs. CD8+ as well as CD4+ T cells became effector T cells recognizing even picomolar concentrations of cognate peptide. TCR-transduced T cells were polyfunctional, secreting the cytokines interferon gamma, tumor necrosis factor alpha and interleukin-2, and effectively killed hepatoma cells replicating HBV. Notably, our collection of HBV-specific TCRs recognized peptides derived from HBV genotypes A, B, C and D presented on different HLA-A*02 subtypes common in areas with high HBV prevalence. When co-cultured with HBV-infected cells, TCR-transduced T cells rapidly reduced viral markers within two days. Our unique set of HBV-specific TCRs with different affinities represents an interesting tool for elucidating mechanisms of TCR-MHC interaction and dissecting specific anti-HBV mechanisms exerted by T cells. TCRs with high functional avidity might be suited to redirect T cells for adoptive T-cell therapy of chronic hepatitis B and HBV-induced hepatocellular carcinoma. |
| format | Article |
| id | doaj-art-36657d80dd584b9cbf50469f96db5884 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-36657d80dd584b9cbf50469f96db58842025-08-20T02:03:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018293610.1371/journal.pone.0182936Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use.Karin WisskirchenKai MetzgerSophia SchreiberTheresa AsenLuise WeigandChristina DargelKlaus WitterElisa KiebackMartin F SprinzlWolfgang UckertMatthias SchiemannDirk H BuschAngela M KrackhardtUlrike ProtzerUlrike ProtzerT-cell therapy of chronic hepatitis B is a novel approach to restore antiviral T-cell immunity and cure the infection. We aimed at identifying T-cell receptors (TCR) with high functional avidity that have the potential to be used for adoptive T-cell therapy. To this end, we cloned HLA-A*02-restricted, hepatitis B virus (HBV)-specific T cells from patients with acute or resolved HBV infection. We isolated 11 envelope- or core-specific TCRs and evaluated them in comprehensive functional analyses. T cells were genetically modified by retroviral transduction to express HBV-specific TCRs. CD8+ as well as CD4+ T cells became effector T cells recognizing even picomolar concentrations of cognate peptide. TCR-transduced T cells were polyfunctional, secreting the cytokines interferon gamma, tumor necrosis factor alpha and interleukin-2, and effectively killed hepatoma cells replicating HBV. Notably, our collection of HBV-specific TCRs recognized peptides derived from HBV genotypes A, B, C and D presented on different HLA-A*02 subtypes common in areas with high HBV prevalence. When co-cultured with HBV-infected cells, TCR-transduced T cells rapidly reduced viral markers within two days. Our unique set of HBV-specific TCRs with different affinities represents an interesting tool for elucidating mechanisms of TCR-MHC interaction and dissecting specific anti-HBV mechanisms exerted by T cells. TCRs with high functional avidity might be suited to redirect T cells for adoptive T-cell therapy of chronic hepatitis B and HBV-induced hepatocellular carcinoma.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182936&type=printable |
| spellingShingle | Karin Wisskirchen Kai Metzger Sophia Schreiber Theresa Asen Luise Weigand Christina Dargel Klaus Witter Elisa Kieback Martin F Sprinzl Wolfgang Uckert Matthias Schiemann Dirk H Busch Angela M Krackhardt Ulrike Protzer Ulrike Protzer Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use. PLoS ONE |
| title | Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use. |
| title_full | Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use. |
| title_fullStr | Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use. |
| title_full_unstemmed | Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use. |
| title_short | Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use. |
| title_sort | isolation and functional characterization of hepatitis b virus specific t cell receptors as new tools for experimental and clinical use |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182936&type=printable |
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