STRUCTURAL STUDIES OF GLYCOLIPID-REACTIVE T CELLS AND ANTIBODIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 CD1家族的抗原提呈分子将多种糖脂抗原呈递给脂类特异性T细胞，导致其激活和扩增，这是执行各种免疫功能所必需的，包括激活其他免疫细胞。对各种CD1-脂质-TCR复合体的结构研究将极大地提高我们对糖脂抗原提呈和免疫系统识别的理解。所获得的结构结果可能用于开发基于脂质的化疗药物或佐剂，以针对各种免疫疾病，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在我们研究所的动物模型中进行评估。在这方面，我们一方面正在研究MS患者中丰富的T细胞，另一方面我们已经用莱姆病的病原体伯氏疏螺旋体的一种潜在的T细胞激动剂结晶了小鼠CD1d。此外，我们还获得了能够区分不同CD1d结合脂类的抗体。CD1d-脂质-Fab之间的三元复合体将提供T细胞和B细胞之间识别和与特定糖脂表位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.