Structure - activity relationships for novel engineered high-affinity T cell receptors

新型工程化高亲和力 T 细胞受体的结构-活性关系

• 批准号: BB/D017726/1
• 负责人: Andrew Sewell
• 金额: $ 18.27万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD017726%2F1
• 关键词: Structure; activity; relationships; novel; engineered

T cell receptors are related to antibodies, but they recognise short processed peptide antigens presented on the cell-surface by specialised proteins. They also have relatively low affinity. Recently, I have succeeded in engineering T cell receptors to have up to 1,000,000 times higher affinity by a process involving display by bacteriophage. These high-affinity T cell receptors have similar characteristics to monoclonal antibodies and have many potential biomedical applications in the treatment of viral infections, cancer and autoimmune diseases. High affinity is generated by several mutations in the T cell receptor sequence but it is currently very unclear exactly how high affinity is generated by these mutations. In this project, I will examine these mutations on an individual basis to build up 'structure - activity relationships' for two published high-affinity T cell receptors. This will provide an insight into how they work and could potentially enable computer prediction of high affinity for T cell receptors in the future.

T细胞受体与抗体有关，但它们识别通过专门蛋白质呈递在细胞表面的短加工肽抗原。它们也具有相对较低的亲和力。最近，我成功地通过噬菌体展示的方法，将T细胞受体的亲和力提高了100万倍。这些高亲和力T细胞受体具有与单克隆抗体相似的特性，并且在治疗病毒感染、癌症和自身免疫性疾病中具有许多潜在的生物医学应用。高亲和力是由T细胞受体序列中的几个突变产生的，但目前还不清楚这些突变到底产生了多高的亲和力。在这个项目中，我将在个体的基础上研究这些突变，以建立两个已发表的高亲和力T细胞受体的“结构-活性关系”。这将提供对它们如何工作的深入了解，并可能在未来实现对T细胞受体高亲和力的计算机预测。