Identification of TAPBPL as a novel negative regulator of T‐cell function
Abstract T cell stimulatory and inhibitory molecules are critical for the regulation of immune responses. In this study, we identify a novel T cell co‐inhibitory molecule TAPBPL, whose amino acid sequence shares homology with known B7 family members. TAPBPL protein is expressed on resting and activa...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2021-05-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202013404 |
| _version_ | 1797282171377942528 |
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| author | Yujun Lin Cheng Cui Min Su Lawrence K Silbart Haiyan Liu Jin Zhao Lang He Yuanmao Huang Dexin Xu Xiaodan Wei Qian Du Laijun Lai |
| author_facet | Yujun Lin Cheng Cui Min Su Lawrence K Silbart Haiyan Liu Jin Zhao Lang He Yuanmao Huang Dexin Xu Xiaodan Wei Qian Du Laijun Lai |
| author_sort | Yujun Lin |
| collection | DOAJ |
| description | Abstract T cell stimulatory and inhibitory molecules are critical for the regulation of immune responses. In this study, we identify a novel T cell co‐inhibitory molecule TAPBPL, whose amino acid sequence shares homology with known B7 family members. TAPBPL protein is expressed on resting and activated T cells, B cells, monocytes, and dendritic cells (DCs), as well as on some tumor tissues. The putative TAPBPL receptor is expressed on activated CD4 and CD8 T cells. A soluble recombinant human TAPBPL‐IgG Fc (hTAPBPL‐Ig) fusion protein inhibits the proliferation, activation, and cytokine production of both mouse and human T cells in vitro. In vivo administration of hTAPBPL‐Ig protein attenuates experimental autoimmune encephalomyelitis (EAE) in mice. Furthermore, an anti‐TAPBPL monoclonal antibody neutralizes the inhibitory activity of hTAPBPL‐Ig on T cells, enhances antitumor immunity, and inhibits tumor growth in animal models. Our results suggest that therapeutic intervention of the TAPBPL inhibitory pathway may represent a new strategy to modulate T cell‐mediated immunity for the treatment of cancer, infections, autoimmune diseases, and transplant rejection. |
| first_indexed | 2024-03-07T17:09:09Z |
| format | Article |
| id | doaj.art-c39273ccefc141c486e0755f1dbd8b8b |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:09:09Z |
| publishDate | 2021-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-c39273ccefc141c486e0755f1dbd8b8b2024-03-03T02:17:20ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-05-01135n/an/a10.15252/emmm.202013404Identification of TAPBPL as a novel negative regulator of T‐cell functionYujun Lin0Cheng Cui1Min Su2Lawrence K Silbart3Haiyan Liu4Jin Zhao5Lang He6Yuanmao Huang7Dexin Xu8Xiaodan Wei9Qian Du10Laijun Lai11Department of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USADepartment of Allied Health Sciences University of Connecticut Storrs CT USAPlant Biology Section Cornell University Ithaca NY USADepartment of Allied Health Sciences University of Connecticut Storrs CT USAAbstract T cell stimulatory and inhibitory molecules are critical for the regulation of immune responses. In this study, we identify a novel T cell co‐inhibitory molecule TAPBPL, whose amino acid sequence shares homology with known B7 family members. TAPBPL protein is expressed on resting and activated T cells, B cells, monocytes, and dendritic cells (DCs), as well as on some tumor tissues. The putative TAPBPL receptor is expressed on activated CD4 and CD8 T cells. A soluble recombinant human TAPBPL‐IgG Fc (hTAPBPL‐Ig) fusion protein inhibits the proliferation, activation, and cytokine production of both mouse and human T cells in vitro. In vivo administration of hTAPBPL‐Ig protein attenuates experimental autoimmune encephalomyelitis (EAE) in mice. Furthermore, an anti‐TAPBPL monoclonal antibody neutralizes the inhibitory activity of hTAPBPL‐Ig on T cells, enhances antitumor immunity, and inhibits tumor growth in animal models. Our results suggest that therapeutic intervention of the TAPBPL inhibitory pathway may represent a new strategy to modulate T cell‐mediated immunity for the treatment of cancer, infections, autoimmune diseases, and transplant rejection.https://doi.org/10.15252/emmm.202013404autoimmune diseaseB7 familyT cellsTAPBPLtumor immunity |
| spellingShingle | Yujun Lin Cheng Cui Min Su Lawrence K Silbart Haiyan Liu Jin Zhao Lang He Yuanmao Huang Dexin Xu Xiaodan Wei Qian Du Laijun Lai Identification of TAPBPL as a novel negative regulator of T‐cell function EMBO Molecular Medicine autoimmune disease B7 family T cells TAPBPL tumor immunity |
| title | Identification of TAPBPL as a novel negative regulator of T‐cell function |
| title_full | Identification of TAPBPL as a novel negative regulator of T‐cell function |
| title_fullStr | Identification of TAPBPL as a novel negative regulator of T‐cell function |
| title_full_unstemmed | Identification of TAPBPL as a novel negative regulator of T‐cell function |
| title_short | Identification of TAPBPL as a novel negative regulator of T‐cell function |
| title_sort | identification of tapbpl as a novel negative regulator of t cell function |
| topic | autoimmune disease B7 family T cells TAPBPL tumor immunity |
| url | https://doi.org/10.15252/emmm.202013404 |
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