Abstract

The purpose of the immune system is to protect our bodies from infection. One way it accomplishes this task is through the presentation of foreign pathogens to NKT cells. After an antigen is presented to the T cell receptor, activated NKT cells quickly release soluble chemical signals, termed chemokines and cytokines, that modulate the response of the immune system. Due to the immunological relevance of NKT cell activation, we developed and synthesised non-natural analogs of immunostimulatory type I, II, and gamma delta NKT cell antigens. The immunological evaluations of these analogs resulted in identification of sulfatide as a gamma delta NKT cell antigen, along with the characterization of these newly discovered sulfatide-reactive gamma delta NKT cell line. During sulfatide structure activity relationship studies, a novel azido-sulfatide analog was synthesized to traffick and image sulfatide in vivo. These studies demonstrated that sulfatide accumulated in the late endosome/lysosome. In conjunction with previous studies, this observation explains the persistence of CD1d-restricted T cells with high affinity for this antigen in healthy individuals. Finally, stimulatory assays were performed on a panel of synthesized lyso-glycosylceramides. This led to the discovery of stimulatory type I NKT cell antigens, alpha-psychosine and alpha-glucopsychosine.

Degree

PhD

College and Department

Physical and Mathematical Sciences; Chemistry and Biochemistry

Rights

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