KIR enrichment at the effector-target cell interface is more sensitive than signaling to the strength of ligand binding
KIR enrichment at the effector-target cell interface is more sensitive than signaling to the strength of ligand binding
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DOI：
10.1002/eji.200323582
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发表时间：
2003-04-01
影响因子：
5.4
通讯作者：
Burshtyn, DN
中科院分区：
文献类型：
--
作者：
Borszcz, PD;Peterson, M;Burshtyn, DN
结合主要组织相容性复合物I类分子的杀伤细胞免疫球蛋白样受体（KIR）可抑制自然杀伤细胞对靶细胞的裂解。许多淋巴细胞受体，包括KIR，在与配体承载细胞的界面处富集。富集对抑制性信号传导的贡献尚未确定。我们现在描述了一种在N端具有增强的绿色荧光蛋白（EGFP）的KIR变体，其可以介导抑制性信号传导，但其富集显著减少。该受体在抑制溶解方面仅比在胞质尾中用EGFP标记的相同KIR稍弱，即使后者与野生型KIR一样广泛富集。还检测到受体减少与靶细胞粘附的能力以及可溶性对应物与细胞表面HLA-C结合的能力存在轻微缺陷。我们的研究结果表明，易于检测受体富集所需的相互作用的强度超过了信号所需的强度。
Target cell lysis by natural killer cells is inhibited by killer cell immunoglobulin-like receptors (KIR) that bind major histocompatibility complex class I molecules. Many lymphocyte receptors, including KIR, become enriched at the interface with ligand-bearing cells. The contribution of the enrichment to inhibitory signaling has not been determined. We now describe a KIR variant with enhanced green fluorescent protein (EGFP) at the N terminus that can mediate inhibitory signaling, but its enrichment is markedly reduced. This receptor is only slightly weaker at inhibiting lysis than the same KIR tagged with EGFP in the cytoplasmic tail, even though the latter enriched as extensively as wild-type KIR. A slight defect was also detected in the ability of the receptor to reduce adhesion to target cells and for binding of a soluble counterpart to cell surface HLA-C. Our findings suggest that the strength of the interaction required to readily detect receptor enrichment exceeds that required for signaling.