The molecular basis for the specificity and signalling through the CD200 paired receptor family

CD200 配对受体家族特异性和信号传导的分子基础

• 批准号: G0601169/1
• 负责人: A Barclay
• 金额: $ 43.67万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601169%2F1
• 关键词: molecular; basis; specificity; signalling; through

The immune system is remarkable in that it can recognise foreign materials such as bacteria and viruses without having encountered them before and make a measured response that leads to their elimination. It can distinguish between small infections at the site of for example a bite, from a viral infection like influenza that calls for all the power of the immune system to be mobilised. This control is effected by white blood cells patrolling the body waiting to react. As mentioned the nature of the responses is highly controlled and this is mediated by interactions of proteins at the surface of the blood cells with other cells. This proposal looks at one class of proteins called ?paired receptors? that have been implicated in virus defence and have the intriguing property that they can give very different signals although the bit that recognises other cells is quite similar. The study focuses on a protein called CD200R that is currently being evaluated as a possible therapeutic target. The aim is to understand the mechanisms involved at a molecular level for this interaction where the detailed information may be applicable to this class of proteins. The importance of understanding the subtleties of these types of interactions was made abundantly obvious in the recent clinical trials of a leukocyte therapeutic target CD28. Here it appears that differences in interactions between two closely related species were sufficient to cause a dramatic life threatening and unexpected response. The type of quantitative molecular analysis in this study will identify parameters involved in determining the signal produced with relevance for therapies involving this type of target and for the general understanding of the immune system. Thus it will have implications in understanding and treating diseases like cancer, infectious diseases and autoimmune disease such as arthritis, diabetes.

免疫系统的非凡之处在于，它可以识别细菌和病毒等异物，而不是以前遇到它们，并做出有节制的反应，导致它们被清除。它可以区分咬伤部位的小感染和像流感这样的病毒感染，后者需要调动免疫系统的所有力量。这种控制是通过白血球在体内巡逻等待反应来实现的。如前所述，反应的性质受到高度控制，这是通过血细胞表面的蛋白质与其他细胞的相互作用来调节的。这项提议着眼于一类被称为配对受体的蛋白质。它们与病毒防御有关，并具有耐人寻味的特性，即它们可以发出截然不同的信号，尽管识别其他细胞的BIT非常相似。这项研究的重点是一种名为CD200R的蛋白质，目前正在评估其可能的治疗靶点。其目的是在分子水平上了解这种相互作用的机制，其中详细的信息可能适用于这类蛋白质。在最近的白细胞治疗靶点CD28的临床试验中，了解这些类型相互作用的微妙之处的重要性变得非常明显。在这里，似乎两个密切相关的物种之间相互作用的差异足以引起戏剧性的生命威胁和意想不到的反应。这项研究中的定量分子分析类型将确定所涉及的参数，以确定与涉及这种类型的靶点的治疗和对免疫系统的一般了解相关的信号产生。因此，它将对理解和治疗癌症、传染病和自身免疫性疾病如关节炎、糖尿病等具有重要意义。