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 （40）抑制等位基因，称为KIR 3DL 1。各种KIR 3DL 1亚型已被证实是 显示与具有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 在这些表达Bw 4的细胞与报道细胞结合之前，在这些细胞中进行应激。我们也 已经确定了KIR 3DS 1的关键残基，这些残基不存在于KIR 3DL 1中。通过诱变， 已经表明KIR 3DS 1的W138与HLA-Bw 4识别的缺乏密切相关 KIR3DS1。在KIR 3DL 1中发现的W138到G的回复赋予Bw 4结合而不影响Bw 4结合。 受体的表达或抗体识别。

KIR3DS1 is presumed to be an NK cell activation receptor. The gene has many (>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. We also have identified key residues of KIR3DS1 that do not exist in KIR3DL1. Through mutagensis we have shown that W138 of KIR3DS1 is critically involved in the lack of recognition of HLA-Bw4 by KIR3DS1. Reversion of W138 to G found in KIR3DL1 confers Bw4 binding without affecting the expression or antibody recognition of the receptor.