Innate immune functions of human gamma-delta T lymphocytes

人γ-δ T淋巴细胞的先天免疫功能

• 批准号: 5357070
• 负责人: Professor Dr. Dietrich Kabelitz
• 金额: --
• 依托单位: Institut für Immunologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5357070?language=en
• 关键词: Innate; immune; functions; human; gamma

T lymphocytes expressing the ab T-cell receptor (TCR) display a broad diversity of TCR germline repertoire, recognize antigen-derived peptides in an MHC class I or class II-restricted manner, and are effector cells of the adaptive cellular immune system. In striking contrast, T lymphocytes expressing the alternative gd TCR have a very restricted TCR germline repertoire, and characteristically recognize phosphorylated intermediates of the bacterial isoprenoid biosynthesis pathway in a non-MHC-restricted and antigen presentation-independent fashion. Thus, it appears that human gd T cells use their TCR as a pattern recognition receptor for the rapid recognition of microbial products that are not seen by other cells of the innate or adaptive immune system. The present proposal will focus on two major goals: (i) To characterize in detail the rapid response of human gd T cells to bacterial phosphoantigens at the level of effector functions (e.g., cytokine production) and signal transduction pathways; and (ii) to investigate in detail the expression and possible function of toll-like receptors (TLR), an additional set of pattern recognition receptors of innate immune cells, on human gd T lymphocytes. These studies will help to clarify the role of human gd T cells as a potential link between the innate and the adaptive immune system.

表达ab T细胞受体（TCR）的T淋巴细胞显示广泛多样的TCR种系库，以MHC I类或II类限制性方式识别抗原衍生肽，并且是适应性细胞免疫系统的效应细胞。与此形成鲜明对比的是，表达替代性gd TCR的T淋巴细胞具有非常有限的TCR种系库，并且特征性地以非MHC限制性和抗原呈递独立性的方式识别细菌类异戊二烯生物合成途径的磷酸化中间体。因此，似乎人gd T细胞使用其TCR作为模式识别受体，用于快速识别先天性或适应性免疫系统的其他细胞看不到的微生物产物。本提案将集中于两个主要目标：（i）详细表征人gd T细胞在效应子功能水平上对细菌磷酸化抗原的快速应答（例如，细胞因子产生）和信号转导途径;和（ii）详细研究Toll样受体（TLR）的表达和可能的功能，TLR是先天免疫细胞的模式识别受体的另一组，在人gd T淋巴细胞上。这些研究将有助于阐明人类gd T细胞作为先天性和适应性免疫系统之间潜在联系的作用。