Receptors and Ligands Regulating Human NK cell Proliferation

一种名为自然杀伤(NK)细胞的白细胞在病毒感染和癌症的早期控制中至关重要。NK细胞杀死患病细胞，并分泌免疫激素(细胞因子)，改变血液细胞和免疫系统的反应方式。当刺激NK细胞分裂时，NK细胞的这些功能明显增强。这个项目试图了解NK细胞的增殖是如何被控制的。识别‘自我’的受体会抑制NK细胞的功能和细胞分裂，从而保护自身并摧毁患病细胞。然而，许多NK细胞既表达抑制受体，也表达激活受体，这是同一种“自身”蛋白。我们将调查是什么决定了这一相互竞争的信息的结果。许多NK细胞受体仍有待鉴定，我们将使用基因表达方法和单克隆抗体来鉴定这些受体，并确定它们如何影响NK细胞的增殖。我们将利用分子工程来构建新的NK细胞受体的多聚体阵列，以寻找它们与其他细胞上相互作用的配体分子。识别NK细胞受体及其调节NK细胞增殖和功能的配体将使我们能够了解这些细胞在健康、炎症性疾病和癌症中的作用。

A white blood cell called a Natural Killer (NK) cell is critical in the early control of viral infections and cancer. NK cells kill the diseased cells and secrete immunological hormones (cytokines) that alter how cells of the blood and immune systems respond. These functions of NK cells are markedly increased when NK cells are stimulated to divide. This project seeks to understand how NK cell proliferation is controlled. Receptors that recognise 'self' inhibit NK cell function and cell division thereby preserving self and destroying diseased cells. Yet many NK cells express both an inhibitory and activating receptor for this same 'self' protein. We will investigate what determines the outcome of this competing information. Many NK cell receptors remain to be identified and we will use a gene expression approach and monoclonal antibodies to identify these and determine how they affect NK cell proliferation. We will use molecular engineering to construct multimeric arrays of new NK cell receptors to search for the ligand molecules that they interact with on other cells. Identifying NK cell receptors and their ligands regulating NK cell proliferation and function will enable us to understand the role of these cells in health and in inflammatory diseases and cancer.