Coordination Funds

协调基金

• 批准号: 412990980
• 负责人: Professor Dr. Immo Prinz
• 金额: --
• 依托单位: Institut für Systemimmunologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/412990980?language=en
• 关键词: Coordination; Funds

Compared with αβ-T cells, the biology of γδ-T cells in health and disease is poorly understood. We know that γδ T cells are highly conserved among vertebrates and that they arise very early in fetal life. γδ T cells exhibit a highly diverse T cell receptor (TCR) repertoire, particularly with respect to their TCR δ-chains. However, it is still not clear how TCR-ligand interactions control thymic selection processes and the formation of the γδ-TCR repertoire in the periphery. This may be because there is currently no overarching concept of how γδ-TCRs are activated by specific antigen and very few γδ-T cell ligands have been identified to date. In the current funding period (three years from 10/2018 - 09/2021), we have established a vibrant network and are sharing protocols, materials, and questions to investigate how signals are received and translated across the γδ TCR. Although the SARS-Cov-2 pandemic forced a partial closure of our research labs for at least three months in early 2020, we have cooperatively built a truly interactive DFG research group. Already, FOR 2799 has an internationally visible scientific output and we are pursuing an ambitious program to disseminate our research results and questions despite these extraordinary times.The main goal of this renewal application is to further join our collective forces to explore how the γδ TCR works and how this knowledge can be used in immunotherapy and potentially as a new tool against infectious diseases. To this end, we have defined three main axes of collaboration:1) We will use experimental models and clinical observations to analyze the role of the γδ TCR in the activation of γδ T cells during an immune response.2) We will use CRISPR/Cas9 sgRNA-based screening assays and to identify novel ligands of the γδ TCR and characterize their mode of γδ TCR activation using structural analyses.3) We will combine an arsenal of pharmacological and biochemical methods to manipulate the γδ TCR and its signal transduction machinery to improve and optimize the efficacy of γδ T cells and γδ TCR constructs for cancer immunotherapy. In a mid- to long-term perspective, the findings of this research group should strongly support translational approaches to the use of γδ TCRs and γδ CARs in immunotherapy.

与 αβ-T 细胞相比，γδ-T 细胞在健康和疾病中的生物学知之甚少。我们知道 γδ T 细胞在脊椎动物中高度保守，并且它们在胎儿生命的早期就出现了。 γδ T 细胞表现出高度多样化的 T 细胞受体 (TCR) 库，特别是在 TCR δ 链方面。然而，目前尚不清楚TCR-配体相互作用如何控制胸腺选择过程和外周γδ-TCR库的形成。这可能是因为目前还没有关于特定抗原如何激活 γδ-TCR 的总体概念，并且迄今为止已鉴定出的 γδ-T 细胞配体很少。在当前资助期间（从 10/2018 到 09/2021 的三年），我们建立了一个充满活力的网络，并共享协议、材料和问题，以研究如何在 γδ TCR 中接收和翻译信号。尽管 2020 年初 SARS-Cov-2 大流行迫使我们的研究实验室部分关闭至少三个月，但我们合作建立了一个真正互动的 DFG 研究小组。 FOR 2799 已经拥有国际知名的科学成果，尽管在这个非常时期，我们仍在推行一项雄心勃勃的计划来传播我们的研究成果和问题。此次更新应用程序的主要目标是进一步加入我们的集体力量，探索 γδ TCR 的工作原理以及如何将这些知识用于免疫治疗以及如何潜在地作为对抗传染病的新工具。为此，我们定义了三个合作主轴：1) 我们将使用实验模型和临床观察来分析 γδ TCR 在免疫反应期间激活 γδ T 细胞中的作用。2) 我们将使用基于 CRISPR/Cas9 sgRNA 的筛选分析，识别 γδ TCR 的新型配体，并使用结构分析表征其 γδ TCR 激活模式。3) 我们将结合 操纵 γδ TCR 及其信号转导机制的药理学和生化方法库，以改善和优化 γδ T 细胞和 γδ TCR 构建体在癌症免疫治疗中的功效。从中长期来看，该研究小组的研究结果应该强烈支持在免疫治疗中使用γδ TCR和γδ CAR的转化方法。