Degree Name

BS

Department

Chemistry and Biochemistry

College

Physical and Mathematical Sciences

Defense Date

2018-05-11

Publication Date

2018-06-05

First Faculty Advisor

Paul B Savage

First Faculty Reader

Jonathon Hill

Honors Coordinator

Merritt Andrus

Keywords

Immunity, NKT, Ligand, Aziridine, Cyclized, CD1d

Abstract

Natural Killer T (NKT) cells are a subset of T cells that express an invariant T cell receptor (TCR) that recognizes lipid antigens in context of the CD1d molecule. CD1d presents both exogenous and endogenous glycolipids on the surface of antigen presenting cells (APCs). Multiple exogenous lipids capable of NKT cell stimulation have been characterized, but confirmed endogenous ligands are relatively few in number. Recently, a-galactosylceramides were shown to be endogenous NKT cell ligands. We have observed that a-galactosylceramides cyclize in acidic conditions. Since the biosynthetic pathway of lipid presentation via CD1d likely passes through the acidic lysosome, we propose that cyclized variants of galactosylceramides that contain either aziridine or dihydro pyrrole on the sphingosine scaffold could be endogenous NKT cell ligands or function as intermediates in b®aisomerization. To verify our hypothesis, we proposed synthesis of six cyclized galactosylceramides. Three out of the six target ligands have been synthesized. Upon completion, we will conduct immunological assays in vivoand in vitroto assess the stimulatory profiles of the ligands towards NKT cells. The outcome of the bioassays will guide our future research and aid in our understanding of NKT cell selection and development.

Handle

http://hdl.lib.byu.edu/1877/uht0038

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Biochemistry Commons

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