Charaterization of the Expression and Ligands of KIR3DS1

KIR 3DS 1被认为是NK细胞活化受体。该基因有许多 （超过40个）抑制等位基因，称为KIR 3DL 1。各种KIR 3DL 1亚型已被证明 与具有Bw 4公共表位的HLA-I蛋白直接相互作用。无论其 KIR 3DS 1与KIR 3DL 1相似，并且在HIV疾病中起着确定的作用， 显示在NK细胞上表达，并且没有描述配体。为了理解 KIR 3DS 1配体结合我们开发了用于KIR 3DS 1接合的报告系统。的 系统使用与T细胞受体ζ信号传导链融合的KIR 3DS 1。另外我们有 建立了表达HLA Bw 4（B5701）的细胞系。这些细胞系感染了 慢病毒载体，并与报道细胞系组合。目前，慢病毒感染 不会导致KIR 3DS 1报告系统的激活。此外，我们还诱导了 在将这些表达Bw 4的细胞与报告细胞结合之前，对它们进行应激。这些 实验正在进行中。最后，我们已经使用了可溶性KIR 3DS 1和KIR 3DL 1蛋白， 使用我们的Bw 4表达系进行流式细胞术实验。热应激和生化应激 迄今尚未导致KIR 3DS 1报告细胞系的激活。无论如何，高 我们先前描述的KIR 3DS 1的频率，以及这种受体的能力， 激活NK细胞并在HIV病毒血症期间维持，表明我们对其进行的解剖 结合特性将为HIV治疗带来令人兴奋的新方法。

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.