Monoclonal antibodies that bind to distinct epitopes on Fc gamma RI are able to trigger receptor function.
Monoclonal antibodies that bind to distinct epitopes on Fc gamma RI are able to trigger receptor function.
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DOI：
10.4049/jimmunol.143.5.1650
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发表时间：
1989-09
影响因子：
4.4
通讯作者：
P. Guyre;R. Graziano;B. A. Vance;P. Morganelli;M. Fanger
中科院分区：
文献类型：
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作者：
P. Guyre;R. Graziano;B. A. Vance;P. Morganelli;M. Fanger
与人 IgG 高亲和力结合的人单核细胞和巨噬细胞 Fc 受体是一种相对分子质量约为 70 kDa 的表面糖蛋白。该受体 (Fc gamma RI) 已使用 mAb 32 进行了部分表征，该 mAb 32 与受体的 Fc 结合域外部结合，但仍然触发 Fc 受体依赖性功能。在这项研究中，我们描述了四种对 Fc gamma RI 具有特异性的新抗体的特性。基于加性和交叉阻断研究，我们得出结论，其中两种抗体（mAb 22 和 44）定义了第三个表位，该表位不同于 mAb 32 和人 IgG Fc 部分的结合位点。每个 Fc gamma RI 特异性杂交瘤都被选择为在细胞表面表达高水平 mAb 的稳定亚系，然后测试该表面 mAb 触发抗体依赖性细胞毒性的能力。当用作 51Cr 释放测定中的靶标时，所有亚系均被人类单核细胞杀死，而除 Fc gamma RI 之外的骨髓 Ag 特异性杂交瘤则未被杀死。我们得出结论，Fc 受体功能是通过与我们定义的 Fc gamma RI 的三个表位结合而触发的。这些 mAb 可用于 Fc gamma RI 的额外表征，并且当掺入肿瘤定向异源抗体时，可以增强人类单核细胞和巨噬细胞对肿瘤细胞的杀伤作用。
The human monocyte and macrophage Fc receptor that binds human IgG with high affinity is a surface glycoprotein with a relative molecular mass of approximately 70 kDa. This receptor (Fc gamma RI) has been partially characterized using mAb 32 which binds outside the Fc binding domain of the receptor, but nonetheless triggers Fc receptor-dependent functions. In this study, we describe the properties of four new antibodies with specificity for Fc gamma RI. Based on additivity and cross-blocking studies, we conclude that two of these antibodies (mAb 22 and 44) define a third epitope which is distinct from the binding sites for both mAb 32 and the Fc portion of human IgG. Each Fc gamma RI-specific hybridoma was selected for stable sublines expressing high levels of mAb on the cell surface, and then tested for the ability of this surface mAb to trigger antibody-dependent cell cytotoxicity. All sublines were killed by human monocytes when used as targets in a 51Cr-release assay, whereas hybridomas specific for myeloid Ag other than Fc gamma RI were not killed. We conclude that Fc receptor function is triggered through binding to each of the three epitopes of Fc gamma RI that we have defined. These mAb will be useful for additional characterization of Fc gamma RI, and may, when incorporated into tumor-directed heteroantibodies, enhance tumor cell killing by human monocytes and macrophages.