Glycans and glycan-binding proteins in immune regulation: A concise introduction to glycobiology for the allergist

Abstract

Cells are endowed with a rich surface coat of glycans that are carried as glycoproteins and glycolipids on the outer leaflets of their plasma membranes and constitute a major molecular interface between cells and their environment. Each cell's glycome, the sum of its diverse glycan structures, comprises a distinct cellular signature defined by expression levels of the enzymes responsible for glycan biosynthesis. This signature can be read by complementary glycan-binding proteins (GBPs) that translate glycan recognition into function. Nowhere is this more evident than in the immune system, where glycans and GBPs are integral to pathogen recognition and control of inflammatory responses. Glycobiology, the study of glycan structures and their functions, increasingly provides insight into immunoregulatory mechanisms and thereby provides opportunities for therapeutic intervention. This review briefly examines the makeup of the human glycome and the GBPs that translate glycan recognition into function and provides examples of glycan recognition events that are responsible for immune system regulation to promote wider appreciation of this rapidly expanding area of research.

Keywords: Glycome; galectin; inflammation; lectin; selectin; sialic acid; siglec.

FIG. 1

Cell surface glycans. All mammalian cells are endowed with a dense and diverse surface coat of glycans comprised of glycoproteins, proteoglycans and glycolipids. They are built primarily from just nine different monosaccharide building blocks, each a six-membered ring with distinct structural substituents. A color-coded symbol nomenclature for these (key) has been agreed upon by the field. N-Linked glycans are attached to protein asparagine residues and are invariably branched structures that display varied termini. O-Linked glycans are attached to protein serine or threonine residues and typically consist of shorter branched or unbranched structures. Proteoglycans are also attached to protein serine or threonine residues, but are notable for their long disaccharide repeats, most of which are highly charged due to the abundance of sugar acids and sulfates. Mammalian glycolipids primarily consist of glycans attached to a ceramide lipid moiety. Together these glycans comprise the glycome of each cell, providing it with the diverse surface structures required for that cell’s functions.

FIG. 2

Representative roles of glycans and glycan binding proteins in immune regulation. (Left panel) Galectin-3 crosslinks T cell receptors (TCR) via their N-linked glycans to regulate immune activation. (Center panel) E- and P-Selectins engage glycans on the surface of passing leukocytes to mediate the initial (tethering) step of inflammation. (Right panel) Siglec-1 (sialoadhesin) captures sialylated pathogens for clearance and antigen presentation, but can be commandeered by HIV for trans-infection and dissemination.