A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity.
A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity.
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DOI：
10.1084/jem.178.3.1121
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发表时间：
1993-09-01
期刊：
影响因子：
--
通讯作者：
Bensussan A
中科院分区：
文献类型：
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作者：
Maïza H;Leca G;Mansur IG;Schiavon V;Boumsell L;Bensussan A
具有自然杀伤 (NK) 活性的人类淋巴细胞，包括大多数活化的 γ/δ+ T 淋巴细胞，无需识别主要组织相容性复合物抗原即可识别并裂解肿瘤靶细胞。然而，与 γ/δ+ T 淋巴细胞不同，NK 细胞不表达 CD3/T 细胞受体 (TCR) 分子，并且参与细胞介导的细胞毒性的受体尚不清楚。为了进一步描述循环 NK 细胞，我们开发了针对人类 NK 白血病 YT2C2 的单克隆抗体 (mAb)。我们报告了一种名为 BY55 的 mAb 的分离，它在细胞表面识别一种表达受限的新型 80-kD 蛋白质。除了免疫细胞系外，该 mAb 还与循环 NK 细胞、γ/δ+ 细胞和一小部分 α/β+ T 淋巴细胞结合。 BY55 mAb 反应性表位/分子的表达受到激活的调节，因为用佛波酯短期培养外周血淋巴细胞 (PBL) 会诱导其下调。此外，未发现 BY55 mAb 与 NK 或与测试的 TCR α/β+ γ/δ+ 克隆有反应性。生化研究和表型分析表明，这种结构与之前在淋巴细胞表面识别的所有分子不同。有趣的是，我们发现 BY55+ 细胞发挥了新鲜循环淋巴细胞获得的大部分 NK 活性。我们报告说，在新鲜的 E 玫瑰花结阳性 PBL 中，只有 CD16+、CD56+ 和 CD57+ 细胞的子集共表达 BY55 分子，表明 BY55 mAb 定义了介导循环 PBL NK 活性的独特子集。
Human lymphocytes with natural killer (NK) activity, including most activated gamma/delta+ T lymphocytes, recognize and lyse tumor target cells without requiring recognition of major histocompatibility complex antigen. However, unlike gamma/delta+ T lymphocytes, NK cells do not express CD3/T cell receptor (TCR) molecules, and the receptors involved in cell-mediated cytotoxicity are unknown. To further delineate circulating NK cells, we developed monoclonal antibodies (mAbs) against the human NK leukemia YT2C2. We report the isolation of a mAb termed BY55, recognizing at the cell surface a novel 80-kD protein with restricted expression. In addition to the immunizing cell line, this mAb binds to circulating NK cells, gamma/delta+ cells, and a minor subset of alpha/beta+ T lymphocytes. Expression of the BY55 mAb- reactive epitope/molecule is regulated by activation, as short-term culture of peripheral blood lymphocytes (PBL) with phorbol ester induced its downmodulation. Furthermore, BY55 mAb reactivity was found neither with the NK nor with the TCR alpha/beta+ gamma/delta+ clones tested. Biochemical studies as well as phenotypic analysis revealed that this structure is different from all previously identified molecules on the lymphocyte cell surface. Interestingly, we found that BY55+ cells exert most NK activity obtained with fresh circulating lymphocytes. We report that within fresh E rosette-positive PBL only a subset of the CD16+, CD56+, and CD57+ cells coexpressed BY55 molecule, indicating that BY55 mAb defines a unique subset mediating NK activity of circulating PBL.