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Systems approach to the analysis of T cell receptor signal transduction

T 细胞受体信号转导分析的系统方法

基本信息

批准号：
MR/J002011/1
负责人：
Philip Van Der Merwe
金额：
$ 52.51万
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：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FJ002011%2F1
关键词：
Systems approach analysis cell receptor

项目摘要

T cells are white blood cells that continuously patrol the body in search of evidence of infection or cancer. Recognition by T cells occurs when receptors on the T cell surface directly bind to fragments or 'antigens' derived from infectious organisms or cancer cells. This recognition is particularly important because T cells, in addition to themselves killing infected or cancerous cells, also coordinate and control other elements of the immune response that are required to remove these threats. T cell antigen recognition is the key to understanding appropriate and helpful immune responses to dangerous antigens (e.g. from harmful bacteria) as well as inappropriate, unhelpful responses to innocuous or self-antigens, which results in allergic and autoimmune diseases, respectively. Although the T cell antigen receptor (TCR) is clearly very important it is still unclear how binding of the TCR to antigen leads to the activation of the T cell and how the TCR detects the rare dangerous antigens amongst the far more numerous harmless antigens. This study aims to address these questions using a systems medicine based approach combining mathematical modelling and range of experimental techniques. An improved understanding of T cell antigen recognition will enhance our ability to manipulate the immune response in order to improve vaccines, treat autoimmune and allergic diseases, and prevent rejection of organ transplants.

T细胞是一种白色血细胞，它不断地在体内巡逻，寻找感染或癌症的证据。当T细胞表面上的受体直接结合来自感染性生物体或癌细胞的片段或“抗原”时，T细胞的识别发生。这种识别特别重要，因为T细胞除了自身杀死感染或癌细胞外，还协调和控制消除这些威胁所需的免疫反应的其他要素。T细胞抗原识别是理解对危险抗原（例如来自有害细菌）的适当和有益的免疫应答以及对无害或自身抗原的不适当、无益的应答的关键，这分别导致过敏性和自身免疫性疾病。尽管T细胞抗原受体（TCR）显然非常重要，但仍不清楚TCR与抗原的结合如何导致T细胞的活化，以及TCR如何在众多无害抗原中检测罕见的危险抗原。本研究旨在解决这些问题，使用系统医学为基础的方法相结合的数学建模和实验技术的范围。对T细胞抗原识别的更好理解将增强我们操纵免疫反应的能力，以改进疫苗，治疗自身免疫性和过敏性疾病，并防止器官移植排斥反应。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Homodimerization of the Lymph Vessel Endothelial Receptor LYVE-1 through a Redox-labile Disulfide Is Critical for Hyaluronan Binding in Lymphatic Endothelium.

DOI：
10.1074/jbc.m116.736926
发表时间：
2016-11-25
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Banerji S;Lawrance W;Metcalfe C;Briggs DC;Yamauchi A;Dushek O;van der Merwe PA;Day AJ;Jackson DG
通讯作者：
Jackson DG

T lymphocytes need less than 3 min to discriminate between peptide MHCs with similar TCR-binding parameters.