The molecular biology and glycobiology of T cell dysfunction in organ specific autoimmunity.
Dr. Demetriou's laboratory focuses on the molecular biology and glycobiology of T cell function in relation to autoimmune diseases. His lab has recently identified beta1,6 N-acetylglucosaminyltransferase V (Mgat5), an enzyme in the Asn (N)-linked protein glycosylation pathway, as a potent negative regulator of T cell activation and autoimmunity in mice (Demetriou et al (2001) Nature 409 733). Mgat5 glycans limit T cell receptor (TCR) clustering at the immune synapse, decrease TCR signaling and reduce T cell proliferation by maintaining the TCR complex within a cell surface multi-valent galectin-glycoprotein lattice that restricts receptor movement in the plane of the membrane. Dr. Demtriou's lab is currently further defining the structure and function of the T cell galectin-glycoprotein lattice and its role in regulating T cell homeostasis and autoimmunity.