Mechanisms and consequences of iNKT cell stimulation by glycolipid antigens from Sphingomonas bacteria

不变的自然杀伤T细胞(/NKT)由于其快速获得效应功能而参与多种免疫反应，特别是在早期阶段。与识别多肽的传统T细胞不同，/NKT细胞识别糖脂，即与脂肪酸相连的糖。然而，直到最近才在鞘氨醇单胞菌中发现了(NKT细胞)的天然抗原，而/NKT细胞缺陷小鼠的细菌清除大大延迟。这一发现使我们第一次能够探索/NKT细胞的抗原特异性反应性在微生物感染背景下的意义。该项目的目的是确定/NKT细胞及其识别的抗原如何参与对单胞菌的保护性反应。这涉及到细菌攻击后抗微生物免疫反应的动力学和机制的研究。此外，还将跟踪细菌来源的/NKT细胞抗原的处理和呈递，并将研究/NKT细胞与各自的抗原呈递细胞的相互作用。此外，还将研究天然细菌抗原对/NKT细胞功能的长期影响。通过对模型病原体Sphingomonas的研究获得的结果将促进对携带/NKT细胞特异性抗原的其他病原体的研究。这项工作将加深我们对NKT细胞生物学和功能的理解，特别是在微生物感染期间，并可能导致新的免疫疗法。

Invariant natural killer T (/NKT) cells have been implicated in diverse immune reactions, especially in the early phases, due to their rapid acquisition of effector functions. In contrast to conventional T cells, which recognize peptides, /NKT cells recognize glycolipids, i.e. sugars linked to fatty acids. However, only very recently have natural antigens for (NKT cells been identified in Sphingomonas bacteria, and /NKT cell deficient mice have a greatly delayed bacteria clearance. This finding allows us, for the first time, to explore the significance of the antigen-specific reactivity of /NKT cells in the context of microbial infections. The aim of this project is to determine how / NKT cells and the antigens they recognize are involved in the protective response to Snhinsomonas bacteria. This involves the investigation of the kinetics and mechanisms of the anti-microbial immune response following bacterial challenge. Furthermore the processing and presentation of bacterial derived /NKT cell antigens will be followed, and the interaction of /NKT cells with the respective antigen-presenting cells will be investigated. In addition the long-term effects of natural bacterial antigens on /NKT cell functions will be examined. Results acquired by studies of the model pathogen Sphingomonas will foster investigations with other pathogens bearing / NKT cell specific antigens. This work will deepen our understanding of /NKT cell biology and function, particular during microbial infections, and could led to novel immunotherapeutics.