与天然配体相比,激动型抗 NKG2D 抗体结构揭示了独特的化学计量学和表位。

IF 5.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
mAbs Pub Date : 2024-01-01 Epub Date: 2024-11-25 DOI:10.1080/19420862.2024.2433121
Daniel Fallon, Ching-Shin Huang, Jingya Ma, Christopher Morgan, Zhaohui Sunny Zhou
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引用次数: 0

摘要

自然杀伤(NK)细胞是先天性免疫系统的效应细胞,通过激活和抑制受体信号来区分健康和异常细胞。NKG2D 是一种在 NK 细胞上表达的同源二聚体激活受体,它能识别由遭受感染、恶性转化、慢性炎症和其他细胞压力的细胞表达的各种压力配体。尽管 NKG2D 配体种类繁多,但它们都以配体与同源二聚体 NKG2D 1:1 的比例不对称地与受体结合。与此相反,正如我们在本文中所报告的,激动抗体 2D3 与 NKG2D 结合时,其抗原结合片段与同源二聚体 NKG2D 的比例为 2:1,而 NKG2D 的表位基本上是不同的。与 NKG2D 天然配体相比,这种结合相互作用表明,可能存在独特的机制来接触这种受体,同时在纳入基于 IgG 的疗法时可能带来益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 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.

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来源期刊
mAbs
mAbs 工程技术-仪器仪表
CiteScore
10.70
自引率
11.30%
发文量
77
审稿时长
6-12 weeks
期刊介绍: mAbs is a multi-disciplinary journal dedicated to the art and science of antibody research and development. The journal has a strong scientific and medical focus, but also strives to serve a broader readership. The articles are thus of interest to scientists, clinical researchers, and physicians, as well as the wider mAb community, including our readers involved in technology transfer, legal issues, investment, strategic planning and the regulation of therapeutics.
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