MONOCLONAL-ANTIBODY AND LIGAND-BINDING SITES OF THE T-CELL ERYTHROCYTE RECEPTOR (CD2)
MONOCLONAL-ANTIBODY AND LIGAND-BINDING SITES OF THE T-CELL ERYTHROCYTE RECEPTOR (CD2)
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DOI：
10.1038/329842a0
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发表时间：
1987-10-29
期刊：
影响因子：
64.8
通讯作者：
SEED, B
中科院分区：
文献类型：
--
作者：
PETERSON, A;SEED, B
人T细胞红细胞受体（CD2抗原）允许胸腺细胞和成熟T细胞通过细胞表面蛋白LFA-3粘附在胸腺上皮和靶细胞上（参考文献1-6）。识别CD2的单克隆抗体既可以阻断粘附，也可以在某些组合下诱导抗原非依赖性T细胞活化7 - 9。我们已经通过快速和普遍适用的突变分析确定了16个抗CD2单克隆抗体的结合位点。结合位点落在三个离散的区域：参与激活和阻断红细胞粘附的抗体结合到第一个区域；阻断粘附的抗体与第二个区域结合；参与激活但不阻止粘附的抗体与第三个区域结合。在前两个区域选择的大量突变导致抗体反应性丧失，也削弱了CD2-LFA-3相互作用。突变病变阻断LFA-3结合与激活抗体阻断病变结合的结果吻合较好，支持该类抗体通过模拟LFA-3结合的作用诱导T细胞活化的观点。当同源结构域对齐时，参与LFA-3结合的CD2序列对应于免疫球蛋白可变区高变序列。
The human T cell erythrocyte receptor (CD2 antigen) allows thymocytes and mature T cells to adhere to thymic epithelium and target cells through a cell surface protein, LFA-3 (refs 1–6). Monoclonal antibodies recognizing CD2 can either block adhesion or, in certain combinations, induce an antigen-independent T cell activation7–9. We have identified the binding sites for 16 monoclonal antibodies against CD2 by a rapid and generally applicable mutational analysis. The binding sites fall in three discrete regions: antibodies that participate in activation and block erythrocyte adhesion bind to the first region; antibodies that block adhesion bind to the second region; and antibodies that participate in activation but do not block adhesion bind to the third region. A large number of mutations selected for loss of antibody reactivity in the first two regions also weaken the CD2–LFA-3 interaction. Good agreement was observed between mutational lesions blocking LFA-3 binding and lesions blocking binding by activating antibodies, which supports the view that such antibodies induce T cell activation by mimicking the effect of LFA-3 binding. CD2 sequences that participate in LFA-3 binding correspond to immunoglobulin variable region hypervariable sequences when the homologous domains are aligned.