Charaterization of the Expression and Ligands of KIR3DS1

KIR3DS1被认为是一种NK细胞活化受体。该基因有许多（超过40个）抑制等位基因，被称为KIR3DL1。各种KIR3DL1亚型已被证明与具有Bw4公共表位的hla - 1蛋白直接相互作用。尽管KIR3DS1与KIR3DL1很相似，并且在HIV疾病中也有明确的作用，但直到最近才发现KIR3DS1在NK细胞上表达，并且没有描述过配体。为了了解KIR3DS1配体的结合，我们开发了一个KIR3DS1结合的报告系统。该系统使用KIR3DS1融合到T细胞受体zeta信号链。此外，我们还建立了表达HLA Bw4 （B5701）的细胞系。这些细胞系被慢病毒载体感染，并与报告细胞系结合。到目前为止，慢病毒感染并没有导致KIR3DS1报告系统的激活。此外，我们在将这些Bw4表达细胞与报告细胞结合之前，对它们进行了应激诱导。这些实验正在进行中。最后，我们利用我们的Bw4表达系在流式细胞术实验中使用了可溶性KIR3DS1和KIR3DL1蛋白。迄今为止，热胁迫和生化胁迫尚未导致KIR3DS1报告系的激活。无论如何，我们之前描述的KIR3DS1的高频率，以及这种受体激活NK细胞并在HIV病毒血症期间维持的能力，表明我们对其结合特征的解剖将导致令人兴奋的HIV治疗新方法。

KIR3DS1 is presumed to be an NK cell activation receptor. The gene has many ( more than 40) inhibitory alleles, known as KIR3DL1. Various KIR3DL1 subtypes have been shown to interact directly with HLA-I proteins with the Bw4 public epitope. Regardless of its similarity to KIR3DL1, and its established role in HIV disease, KIR3DS1 has only recently been shown to be expressed on NK cells and no ligand has been described. Toward an understanding of KIR3DS1 ligand binding we developed a reporter system for the engagement of KIR3DS1. The system uses KIR3DS1 fused to the T cell receptor zeta signaling chain. In addition, we have established HLA Bw4 (B5701) expressing cell lines. These cell lines are infected with lentiviral vectors and combined with the reporter line. Thus far, lentiviral infection does not result in the activation of the KIR3DS1 reporter system. In addition, we have induced stress in these Bw4 expressing cells before combining them with the reporter cells. These experiments are on going. Lastly, we have employed soluble KIR3DS1 and KIR3DL1 proteins in flow cytometry experiments using our Bw4 expressing lines. Heat stress, and biochemical stress have thus far not lead to the activation of the KIR3DS1 reporter lines. Regardless, the high frequency of KIR3DS1 we have previously described, together with this receptors ability to activate NK cells and be maintained during HIV viremia, suggest that our dissection of its binding characteristics will lead to exciting new approaches to HIV therapy.