T Cell Receptor Sugar

Abstract

The α and β chains of the T cell receptor (TCR) are modified by N -glycans, and Demetriou et al. now report that these sugars may be inhibitory to TCR activation. T cells were isolated from mice that did not express β-1,6- N -acetylglucosaminyltransferase V (Mgat5), an enzyme of the N -glycosylation pathway. Interaction of TCRs with lectins on the cell surface was lost in the mutant cells. The deficiency resulted in T cells with increased ligand-dependent TCR aggregation as well as enhanced consequential cytoskeletal modifications and stimulation of downstream signaling events including Akt/protein kinase B activation and mobilization of intracellular calcium. The authors suggest that the Mgat5-modified glycans may either sterically limit TCR cluster formation in the membrane or may promote TCR binding to cell surface lectins, hence restricting TCR mobility and clustering. Modification of glycans by Mgat5 and the presence of lectins at the cell surface may dampen TCR sensitivity to antigen. The authors suggest that regulation of receptors in general may be achieved through interaction between sugar residues and lectins. M. Demetriou, M. Granovsky, S. Quaggin, J.W. Dennis, Negative regulation of T-cell activation and autoimmunity by Mgat5 N -glycosylation. Nature 409 , 733-738 (2001). [Online Journal]