T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density
T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density
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DOI：
10.1093/intimm/11.5.777
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发表时间：
1999-05-01
影响因子：
4.4
通讯作者：
Stockinger, H
中科院分区：
文献类型：
--
作者：
Koch, C;Staffler, G;Stockinger, H
CD 147是IG超家族的广泛表达的细胞表面糖蛋白，其表达在T细胞活化时上调。为了阐明CD 147在T细胞生物学中的可能作用，我们建立了15个特异性mAb，通过mAb panel确定了7个不同的表位。大多数mAb仅结合植物血凝素（PHA）活化的T细胞，而不结合静息T细胞。我们证明，这不是因为活化依赖性新表位的真实表达，而是由于相对低亲和力mAb（亲和力常数KA值在2.25 × 10（8）和7 × 10（9）M-1之间）与活化T细胞上更密集表达和/或更聚集的CD 147分子的二价结合。相反，具有较高亲和力（KA > 7 × 10（9）M-1）的mAb甚至可以以单价方式稳定地结合静息T细胞上相对低密度的CD 147分子。这个模型可能更普遍地解释了以前在其他白细胞表面分子中描述的“激活表位”的性质。最后，我们提供的证据表明，通过针对独特表位的mAb诱导CD 147的有序二聚化导致对CD 3介导的T细胞活化的强烈抑制。
CD147 is a broadly expressed cell surface glycoprotein of the Ig superfamily whose expression is upregulated upon T cell activation. In order to elucidate a possible role of CD147 in T cell biology, we established 15 specific mAb, Seven distinct epitopes were defined by the mAb panel. Most of the mAb bound only to phytohemagglutinin (PHA)-activated but not resting T cells. We demonstrate that this was not because of true expression of activation-dependent neoepitopes but rather due to bivalent binding of the relatively low-affinity mAb (affinity constant KA values between 2.25 x 10(8) and 7 x 10(9) M-1) to the more densely expressed and/or more clustered CD147 molecules on the activated T cells. In contrast, the mAb with higher affinity(KA > 7 X 10(9) M-l) could stably bind in a monovalent fashion even to the relatively low dense CD147 molecules on resting T cells. This model might more generally explain the nature of 'activation epitopes' described previously in other leukocyte surface molecules. Finally, we provide evidence that induction of ordered dimerization of CD147 by a mAb directed to a unique epitope results in strong inhibition of CD3-mediated T cell activation.