NK Receptors and CD1 Roles in NK and NK T Cell Function

描述：（改编自申请人的摘要）鼠CD 1分子具有 将糖脂呈递给NK T细胞的能力。NK T细胞是淋巴细胞亚群 其特征在于表达不变的TCR，自身反应性 CD 1分子，以及快速产生大量IFN γ和/或IFN-γ的能力。 IL-4刺激后。NK T细胞参与了多种 免疫应答，包括对肿瘤、感染因子和 自身免疫性疾病进展的调节。我们假设CD 1介导的 NK T细胞反应可能受抑制性和活化性NK细胞的调节。 NK T细胞表达的受体。我们建议描述 抑制和激活小鼠NK T细胞上NK受体的表达以及NK T细胞杂交瘤。此外，还将检测一系列NK受体， 它们调节由CD 1分子诱导的NK T细胞活化的能力， 将其转化为NK T细胞杂交瘤。杂交瘤的特异性 被很好地表征，并且刺激抗原信号的强度可以 通过操纵APC上表达的CD 1的量来调节， 使用的脂聚糖抗原。实验也将进行与小学 NK T细胞研究这些NK受体如何在免疫系统中起作用。 在体内和体外的反应。虽然已知NK受体与MHC反应， 编码I类分子，我们有了令人惊讶的发现， NK细胞通过与CD 1的相互作用而被抑制，尽管CD 1仅在NK细胞中非常小。 与MHC I类分子远亲。因此，几种策略 将进行鉴定CD 1结合NK受体，我们将 确定这些细胞是否作为NKT细胞的辅助受体。 分子作为活化分子通过NK T细胞上的TCR和作为免疫调节剂。 将研究通过NK细胞上的抑制性受体的抑制性分子 在小鼠的鼠巨细胞病毒感染的情况下。这种病毒 在小鼠肝脏中复制，肝脏是一种特别富含NK细胞和NK T的器官 细胞和肝细胞上具有大量的CD 1分子。这些新的研究 将提供深入了解：特异性和免疫调节作用的NK细胞 CD 1反应性NK T细胞和NK细胞上的受体，并提供策略 来调节这一类重要的免疫细胞反应。

DESCRIPTION: (Adapted from applicant's abstract) Murine CD1 molecules have the ability to present glycolipids to NK T cell. NK T cells are a lymphocyte subset that is characterized by the expression of an invariant TCR, autoreactivity to CD1 molecules, and the ability to rapidly produce large amounts of IFNy and/or IL-4 following stimulation. NK T cells have been implicated in a variety of immune responses, including the response to tumors, infectious agents and the regulation of autoimmune disease progression. We hypothesize that CD1 mediated NK T cell responses may be regulated by the inhibitory and activating NK receptors expressed by NK T cells. We propose to characterize the pattern of expression of inhibiting and activating NK receptors on mouse NK T cells and NK T cell hybridomas. In addition, a series of NK receptors will be tested for their ability to regulate the NK T cell activation induced by CD1 molecules, by transfecting them into NK T cell hybridomas. The specificity of the hybridomas is well characterized, and the strength of the stimulating antigen signal can be regulated by manipulating the amount of CD1 expressed on the APC, the amount of lipoglycan antigen used. Experiments also will be carried out with primary NK T cells to study how these NK receptors act in the context of immune responses in vivo and in vitro. While NK receptors are known to react with MHC encoded class I molecules, we have made the surprising finding that a subset of NK cells are inhibited by interaction with CD1, although CD1 is only very distantly related to the MHC class I molecules. Therefore, several strategies will be undertaken to identify the CD1 binding NK receptor(s), and we will determine if these act as co-receptors for the NKT cell .The dual role of CD1 molecule as an activating molecule through the TCR on NK T cells and as an inhibitory molecule through an inhibitory receptor on NK cells will be studied in the context of the murine cytomegalovirus infection of mice. This virus replicates in murine liver, an organ particularly rich in NK cell and NK T cells and with high amount of CD1 molecules on hepatocytes. These novel studies will provide insights into the: specificity and immunoregulatory role of NK receptors on both CD1 reactive NK T cells and NK cells, and provide strategies for the regulation of this important category of immune cell responses.