Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity.
Hepatitis C Virus (HCV) is a major public health concern, with no effective vaccines currently available and 3% of the world's population being infected. Despite the existence of both B- and T-cell immunity in HCV-infected patients, chronic viral infection and HCV-related malignancies progress....
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001018&type=printable |
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| author | Yi Zhang Yeuying Liu Kelly M Moxley Lucy Golden-Mason Lucy Golden-Mason Michael G Hughes Tongxin Liu Mirjam H M Heemskerk Hugo R Rosen Michael I Nishimura |
| author_facet | Yi Zhang Yeuying Liu Kelly M Moxley Lucy Golden-Mason Lucy Golden-Mason Michael G Hughes Tongxin Liu Mirjam H M Heemskerk Hugo R Rosen Michael I Nishimura |
| author_sort | Yi Zhang |
| collection | DOAJ |
| description | Hepatitis C Virus (HCV) is a major public health concern, with no effective vaccines currently available and 3% of the world's population being infected. Despite the existence of both B- and T-cell immunity in HCV-infected patients, chronic viral infection and HCV-related malignancies progress. Here we report the identification of a novel HCV TCR from an HLA-A2-restricted, HCV NS3:1073-1081-reactive CTL clone isolated from a patient with chronic HCV infection. We characterized this HCV TCR by expressing it in human T cells and analyzed the function of the resulting HCV TCR-transduced cells. Our results indicate that both the HCV TCR-transduced CD4(+) and CD8(+) T cells recognized the HCV NS3:1073-1081 peptide-loaded targets and HCV(+) hepatocellular carcinoma cells (HCC) in a polyfunctional manner with cytokine (IFN-gamma, IL-2, and TNF-alpha) production as well as cytotoxicity. Tumor cell recognition by HCV TCR transduced CD8(-) Jurkat cells and CD4(+) PBL-derived T cells indicated this TCR was CD8-independent, a property consistent with other high affinity TCRs. HCV TCR-transduced T cells may be promising for the treatment of patients with chronic HCV infections. |
| format | Article |
| id | doaj-art-52aa547cdf234f33a0cd08927f35c3f2 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2010-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-52aa547cdf234f33a0cd08927f35c3f22025-08-20T02:02:01ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-07-0167e100101810.1371/journal.ppat.1001018Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity.Yi ZhangYeuying LiuKelly M MoxleyLucy Golden-MasonLucy Golden-MasonMichael G HughesTongxin LiuMirjam H M HeemskerkHugo R RosenMichael I NishimuraHepatitis C Virus (HCV) is a major public health concern, with no effective vaccines currently available and 3% of the world's population being infected. Despite the existence of both B- and T-cell immunity in HCV-infected patients, chronic viral infection and HCV-related malignancies progress. Here we report the identification of a novel HCV TCR from an HLA-A2-restricted, HCV NS3:1073-1081-reactive CTL clone isolated from a patient with chronic HCV infection. We characterized this HCV TCR by expressing it in human T cells and analyzed the function of the resulting HCV TCR-transduced cells. Our results indicate that both the HCV TCR-transduced CD4(+) and CD8(+) T cells recognized the HCV NS3:1073-1081 peptide-loaded targets and HCV(+) hepatocellular carcinoma cells (HCC) in a polyfunctional manner with cytokine (IFN-gamma, IL-2, and TNF-alpha) production as well as cytotoxicity. Tumor cell recognition by HCV TCR transduced CD8(-) Jurkat cells and CD4(+) PBL-derived T cells indicated this TCR was CD8-independent, a property consistent with other high affinity TCRs. HCV TCR-transduced T cells may be promising for the treatment of patients with chronic HCV infections.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001018&type=printable |
| spellingShingle | Yi Zhang Yeuying Liu Kelly M Moxley Lucy Golden-Mason Lucy Golden-Mason Michael G Hughes Tongxin Liu Mirjam H M Heemskerk Hugo R Rosen Michael I Nishimura Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. PLoS Pathogens |
| title | Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_full | Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_fullStr | Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_full_unstemmed | Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_short | Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_sort | transduction of human t cells with a novel t cell receptor confers anti hcv reactivity |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001018&type=printable |
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