Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands
Natural killer (NK) cells are effector cells of the innate immune system that distinguish between healthy and abnormal cells through activating and inhibitory receptor signaling. NKG2D, a homodimeric activating receptor expressed on NK cells, recognizes a diverse class of stress ligands expressed by...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2433121 |
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| author | Daniel Fallon Ching-Shin Huang Jingya Ma Christopher Morgan Zhaohui Sunny Zhou |
| author_facet | Daniel Fallon Ching-Shin Huang Jingya Ma Christopher Morgan Zhaohui Sunny Zhou |
| author_sort | Daniel Fallon |
| collection | DOAJ |
| description | Natural killer (NK) cells are effector cells of the innate immune system that distinguish between healthy and abnormal cells through activating and inhibitory receptor signaling. NKG2D, a homodimeric activating receptor expressed on NK cells, recognizes a diverse class of stress ligands expressed by cells experiencing infection, malignant transformation, chronic inflammation, and other cellular stresses. Despite the variety of NKG2D ligands, they all bind the receptor asymmetrically in a 1:1 ligand to homodimeric NKG2D stoichiometry. In contrast, as we report herein, the agonistic antibody 2D3 binds NKG2D with a 2:1 stoichiometry of its antigen binding fragments to homodimeric NKG2D and a largely distinct epitope. This binding interaction, as compared to NKG2D natural ligands, suggests there may be unique mechanisms to engage this receptor while offering possible benefits when incorporated into an IgG-based therapeutic. |
| format | Article |
| id | doaj-art-226c08477f9a4a3aac1f4727a2361136 |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-226c08477f9a4a3aac1f4727a23611362025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2433121Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligandsDaniel Fallon0Ching-Shin Huang1Jingya Ma2Christopher Morgan3Zhaohui Sunny Zhou4Dragonfly Therapeutics, Inc., Waltham, MA, USADragonfly Therapeutics, Inc., Waltham, MA, USADragonfly Therapeutics, Inc., Waltham, MA, USADragonfly Therapeutics, Inc., Waltham, MA, USADepartment of Chemistry and Chemical Biology, Barnett Institute for Chemical and Biological Analysis, Northeastern University, Boston, MA, USANatural killer (NK) cells are effector cells of the innate immune system that distinguish between healthy and abnormal cells through activating and inhibitory receptor signaling. NKG2D, a homodimeric activating receptor expressed on NK cells, recognizes a diverse class of stress ligands expressed by cells experiencing infection, malignant transformation, chronic inflammation, and other cellular stresses. Despite the variety of NKG2D ligands, they all bind the receptor asymmetrically in a 1:1 ligand to homodimeric NKG2D stoichiometry. In contrast, as we report herein, the agonistic antibody 2D3 binds NKG2D with a 2:1 stoichiometry of its antigen binding fragments to homodimeric NKG2D and a largely distinct epitope. This binding interaction, as compared to NKG2D natural ligands, suggests there may be unique mechanisms to engage this receptor while offering possible benefits when incorporated into an IgG-based therapeutic.https://www.tandfonline.com/doi/10.1080/19420862.2024.2433121NKG2Dantibody agonistnatural killer cellsSPRX-ray crystallography |
| spellingShingle | Daniel Fallon Ching-Shin Huang Jingya Ma Christopher Morgan Zhaohui Sunny Zhou Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands mAbs NKG2D antibody agonist natural killer cells SPR X-ray crystallography |
| title | Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands |
| title_full | Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands |
| title_fullStr | Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands |
| title_full_unstemmed | Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands |
| title_short | Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands |
| title_sort | agonistic anti nkg2d antibody structure reveals unique stoichiometry and epitope compared to natural ligands |
| topic | NKG2D antibody agonist natural killer cells SPR X-ray crystallography |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2433121 |
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