STRUCTURAL STUDIES OF GLYCOLIPID-REACTIVE T CELLS AND ANTIBODIES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.