Glycosylation and the Immune System

Abstract

A full understanding of the implications of glycosylation for the structure and function of any glycoprotein can only be reached when the molecule is viewed in its entirety. Many glycoproteins are involved in the humoral and cellular immune systems and can, by virtue of their individual protein structures, influence the processing of their sugars. The sugars provide a range of functions for the proteins to which they are attached. These include stabilising the protein structure, modifying the activity of effector functions, orienting the protein on the cell surface, shielding the protein from proteases and providing specific epitopes for recognition events both in the glycoprotein folding process and on fully folded proteins. NMR solution and X-ray crystallography studies of glycoproteins do not normally yield detailed information about the sugars. In this review we discuss a range of molecules which operate in the immune system and in which protein structural data have been complemented by data from glycan analyses and the dimensions of the sugars taken from the Glycobiology Institute's oligosaccharide structural data base. In this way it has been possible to obtain a more complete view of each glycoprotein and of the proposed functions of the sugars. The glycoproteins include the immunoglobulins IgG, IgA and IgM which are involved in the humoral immune response. IgG and IgM activate the complement system which is controlled by a number of inhibitors, including CD59 and decay accelerating factor (DAF, CD55) which we also discuss. Examples of proteins involved in the cellular immune response include the cell adhesion molecules CD2 and CD48 which mediate the precise alignment of the cell surfaces of cytolytic T-lymphocytes carrying the T-cell receptor (TCR) complex with those of target cells carrying HLA class 1 molecules loaded with peptide.