Charaterization of the Expression and Ligands of KIR3DS1

我们研究了KIR3DS1与HLABw4 80I相互作用的可能性。令人惊讶的是，与多种HIV衍生多肽折叠的HLA四聚体不与KIR3DS1相互作用。KIR3DS1的抑制等位基因KIR3DL1以一种多肽依赖的方式与Bw4结合，这表明KIR3DS1的结合可能需要鉴定合适的多肽。最重要的是，我们首次证明了KIR3DS1通过被单抗Z27识别而在相当一部分外周NK细胞上表达。在KIR3DS1纯合子供者中，多达70%的NK细胞表达该受体。此外，我们还发现KIR3DS1可以在一些个体的NK/T细胞上表达，这表明该受体也可以调节这一群体。此外，为了定义其表达，我们现在已经证明，Z27连接KIR3DS1会导致NK细胞干扰素伽马的产生和脱颗粒。此外，我们还记录了KIR3DS1+NK细胞在HIV病毒症患者中的持久性。KIR3DS1的高频率表达，以及其激活NK细胞的能力和在HIV病毒血症期间的维持，有力地支持了流行病学数据，表明KIR在HIV发病机制中起着关键作用。

We have studied the potential for KIR3DS1 interactions with HLA Bw4 80I. Surprisingly, HLA tetramers folded with a variety of HIV-derived peptides did not interact with KIR3DS1. The inhibitory allele of KIR3DS1, KIR3DL1, binds Bw4 in a peptide-dependent manner suggesting that KIR3DS1 binding may require identification of the appropriate peptide. Most importantly, we have demonstrated for the first time KIR3DS1 expression on a substantial portion of peripheral NK cells through its recognition by the monoclonal antibody Z27. In donors homozygous for KIR3DS1 as many as 70% of NK cells express the receptor. Moreover, we have found that KIR3DS1 can be expressed on the NK/T cells of some individuals suggesting the receptor can regulate that population as well. In addition, to defining its expression, we have now shown that ligation of KIR3DS1 by Z27 leads to NK cell interferon gamma production and degranulation. Furthermore, we have documented the persistence of KIR3DS1+ NK cells in HIV viremic patients. The high frequency of KIR3DS1 expression, together with its ability to activate NK cells and its maintenance during HIV viremia, strongly support the epidemiological data suggesting a critical role for this KIR in HIV pathogenesis.