Roles for glycosylation of cell surface receptors involved in cellular immune recognition

The majority of cell surface, receptors involved in antigen recognition by T cells and in the orchestration: of the subsequent cell signalling events are glycoproteins. The length of a typical N-linked sugar is comparable wit h that of an immunoglobulin domain (30 Angstrom). Thus, by virtue of their size alone,oligosaccharides may be expected to play a significant role in t he functions and prop erties of the cell surface proteins to which they are attached. A databank of oligosaccharide structures has been constructed fr om NMR and crystallographic data to aid in the interpretation of crystal st ructures of glycoproteins. As unambiguous electron density can usually only be assigned to the glycan cores, the remainder of the sugar is then modell ed into the crystal latticeby superimposing the appropriate oligosaccharide from the database. This approach provides insights into the roles that gly cosylation might play in cell surface receptors, by providing models that d elineate: potential close packing interactions on the cell surface. It has been proposed that the specific recognition of antigen by T cells results i n the formation of an immunological synapse between the T cell and the anti gen-presenting cell. The cell adhesion glycoproteins, such as CD2 and CD48, help to form a cell junction, providing a molecular spacer between opposin g cells. The oligosaccharides located on the membrane proximal domains of C D2 and CD48 provide a scaffold to orient the binding faces, which leads to increased affinity. In the next step, recruitment of thepeptide major histo compatibility complex (pMHC):by the T-cell receptors (TCRs) requires mobili ty on the membrane surface. The TCR sugars are located such that they could prevent non-specific aggregation, importantly, the sugars limitthe possibl e geometry and spacing of TCR/MHC clusters which precede cell signalling. W e postulate that, in the final stage, the sugars could play a generalrole i n controlling the assembly and stabilisation of the complexes in the synaps e and in protecting them from proteolysis! during prolonged T-cell engageme nt. (C) 1999 Academic Press.