Seminar

The Glycocalyx as a Nexus of Control Over Human T cell Immunophysiology

Landon Edgar

All cell surfaces are densely functionalized by oligomers of carbohydrates called glycans that collectively form the glycocalyx. These structurally complex biomolecules are displayed on membrane proteins and lipids but are not directly encoded in the genome. We have recently reported that specific types of glycans called sialoglycans (SGs) play important regulatory roles on T cells; however, the specific mechanisms through which SGs exert these functions remain unknown. We now have data confirming that many functionally important protein-protein interactions that are required for T cell activation are sensitive to the specific glycan content of the T cell glycocalyx. Our experimental approach includes newly developed technologies for the unbiased characterization of glycan binding capacity across the T cell surface proteome. We have also mechanistically dissected the contributions of glycans to human T cell immunophysiology using phosphoproteomic and transcriptomic approaches. These results show that specific glycan structures greatly influence intracellular signalling cascades and connect glycocalyx composition to fine regulation of the central dogma of biology. We demonstrate that artificial editing of T cell glycans provides new dimensions of control over their phenotype and function. Finally, we describe how disruption of T cell glycosylation is a feature of a T cell-driven human autoimmune disease and showcase our preliminary efforts to correct glycosylation defects to improve human health.