Differential binding to HLA-C of p50-activating and p58-inhibitory natural killer cell receptors
Differential binding to HLA-C of p50-activating and p58-inhibitory natural killer cell receptors
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DOI：
10.1073/pnas.95.24.14326
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发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Strominger, J
中科院分区：
文献类型：
--
作者：
Valés-Gómez, M;Reyburn, HT;Strominger, J
自然杀伤（NK）细胞的细胞毒性在很大程度上受能够结合I类主要组织相容性复合物糖蛋白的NK细胞受体的表达调节。与识别HLA-C同种异体特异性相关的受体是两个结构域的Ig样分子，p50和p58蛋白，具有高度同源的胞外结构域，但不同之处在于它们分别具有激活或抑制功能，这取决于它们所具有的跨膜结构域和胞质尾区。我们比较了抑制性p58分子NKAT 2、高度同源的激活性p50分子克隆49和第二激活性p50分子克隆39与HLA-Cw 7的结合，克隆39与NKAT 1和NKAT 2都具有同源性。NKAT 2以非常快的结合和解离速率与HLA-Cw 7结合。然而，p50受体与HLA-C的结合非常弱，如果有的话。这种差异的分子基础进行了分析，并讨论了这些意见的功能意义。
Natural killer (NK) cell cytotoxicity is regulated in large part by the expression of NK cell receptors able to bind class I major histocompatibility complex glycoproteins. The receptors associated with recognition of HLA-C allospecificities are the two-domain Ig-like molecules, p50 and p58 proteins, with highly homologous extracellular domains but differing in that they have either an activating or inhibitory function, respectively, depending on the transmembrane domain and cytoplasmic tails that they possess. We have compared the binding to HLA-Cw7 of an inhibitory p58 molecule, NKAT2, the highly homologous activating p50 molecule, clone 49, and a second activating p50 molecule, clone 39, which has homologies to both NKAT1 and NKAT2. NKAT2 binds to HLA-Cw7 with very rapid association and dissociation rates. However, the p50 receptors bind only very weakly, if at all, to HLA-C. The molecular basis of this difference is analyzed, and the functional significance of these observations is discussed.