STRUCTURAL STUDIES OF GLYCOLIPID-REACTIVE T CELLS AND ANTIBODIES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 抗原呈递分子的CD 1家族向脂质特异性T细胞呈递多种糖脂抗原，导致其活化和扩增，这是进行各种免疫功能（包括其他免疫细胞的活化）所必需的。各种CD 1-脂质-TCR复合物的结构研究将极大地增强我们对免疫系统中糖脂抗原呈递和识别的理解。所获得的结构结果可以潜在地用于开发基于脂质的化疗剂或佐剂，以靶向各种免疫病症，例如多发性硬化症（MS）或莱姆病。这些化合物的免疫调节功能可以使用本研究所的动物模型进行评估。在这方面，我们一方面正在研究MS患者中富集的T细胞，另一方面我们已经用莱姆病病原体Borrelia burgdorferi的潜在T细胞激动剂结晶了小鼠CD 1d。此外，我们已经获得了抗体，可以区分不同的CD 1d结合的脂质。CD 1d-脂质-Fab B之间的三元复合物将提供T细胞和B细胞之间与特定糖脂表位的识别和相互作用的详细比较。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The CD1 family of antigen presenting molecules presents a wide variety of glycolipid antigens to lipid-specific T cells, resulting in their activation and expansion, necessary to carry out various immune functions including the activation of other immune cells. Structural studies of various CD1-lipid-TCR complexes will greatly enhance our understanding of glycolipid antigen presentation and recognition in the immune system. The gained structural results can potentially be used for the development of lipid based chemotherapeutic agents or adjuvants to target various immune conditions, such as Multiple Sclerosis (MS) or lyme disease. The immunomodulatory functions of these compounds can be assessed using animal models in our institute. In that regard we are working on one hand with T cells that are enriched in MS patients and on the other hand we have already crystallized mouse CD1d with a potential T cell agonist from Borrelia burgdorferi, the causative agent of Lyme disease. Furthermore we have obtained antibodies, which can discriminate between different CD1d-bound lipids. A ternary complex between CD1d-lipid-Fab will provide a detailed comparison of the recognition and interaction with specific glycolipid epitopes between T cells and B cells.