Antigens: Carbohydrates II

Abstract

Glycosylation is critical for a wide range of biological processes across both normal and disease states. Carbohydrate antigens, for example, are polymeric chains of diverse monomeric sugar molecules that play a fundamental role in the pathogenicity and virulence of many organisms. Moreover, these pathogen‐associated glycan structures can also be found in association with other types of cells, including tumours. These types of glycan commonalities have helped generate critical discoveries in terms of glycan structure, allowing for the development of working hypotheses for their functions, in addition to the development of agents that target or mediate their expression levels. Therefore, through discussion of glycans as antigens, new insights of key molecular and cellular interactions between them and immune cells can be discerned, and the implication of these interactions in health and disease is enhanced. Numerous reviews and even this ELS series have described the structure of carbohydrates and glycans in general.

Key Concepts

  • Glycosylation is the most abundant post‐translational modification of proteins.
  • Glycans expand the chemical diversity of the genetic code.
  • Antigens are a collection of epitopes that affects recognition by the immune system.
  • Antigens and immunogens are very different.
  • Molecular mimicry of glycans profoundly affects the pathophysiology of infection and neoplasia.
  • Lectin‐family receptors and antibodies have been used to define carbohydrate antigens.
  • Clustering of epitopes defines glycan antigens better than nonclustered epitopes.
  • Carbohydrate antigens can define danger signals to the immune system through pattern recognition receptors.
  • Clustering associates with different B‐cell populations for processing as immunogens.
  • MHC and T‐cell receptors see atoms in particular arrays, not as a single molecular species – hence cross‐reactivity with zwitterionic carbohydrate structures.
  • While carbohydrate‐based vaccines have been developed, as cancer vaccines they are not as effective.
  • Metabolism is the next frontier to understanding glycan expression patterns.

Keywords: carbohydrates; glycans; antigens; immunogens; neutral glycolipids; ganglioside; N‐linked glycoproteins; O‐linked glycoproteins; polysialic acids; histo‐blood group; danger signal; zwitterionic; B‐cell; T‐cell; vaccines; immune system; innate immune; adaptive immune; glycomics

Figure 1. Characteristics of an antigen moving to vaccine development. There are many considerations as we move from defining an antigen to making a vaccine. In general, carbohydrate‐based vaccines have fundamentally more challenges than protein‐based vaccines.
Figure 2. Rudimentary characteristics of all cells and organisms. DNA forms the genome, RNA forms the transcriptome, proteins form the proteome, enzymes and energy flux form the metabolome, lipids form the lipidome, with the accumulation of glycans at the cell surface and those secreted forming the glycome.
Figure 3. Common monosaccharide's that form polysaccharides. Polysaccharides and oligosaccharides are also known as glycans. Polysaccharides are long chains of common monosaccharides linked by glycosidic bonds.
Figure 4. Glycans permeate all biological processes. Glycans influence human health, protein folding and intracellular transport, and form the basis for new drug and diagnostic development.
Figure 5. Examples depicting similarity of epitopes in dissimilar carbohydrate upon super‐positioning of antigens. In (a) Ley antigen on left side of top panel with MCP on right side of top panel. Superpositioning of Ley with MCP (third panel in A indicate that methyl group in blue and hydroxyls in red define a common epitope. If an antibody recognised the common epitope it could not distinguish MCP from Ley. (b) Likewise, a common epitope is defined on the Ley antigen on left side of first panel with α1–4 Glucose on right side of the first panel. Super‐positioning (second panel) highlights that the defined epitope in glucose is formed by hydroxyls on different sugars.
Figure 6. Structures of bacterial zwitterionic polysaccharides adapted from Nishat and Andreana (Nishat and Andreana, ). A1 (PS A1) and PS B from Bacteroides fragilis, PS A2 from Bacteroides fragilis 638R, specific type 1 polysaccharide (Sp1) from Streptococcus pneumoniae, and CP5/CP8 from Staphylococcus aureus.
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Kieber‐Emmons, AnnMarie, Monzavi‐Karbassi, Behjatolah, and Kieber‐Emmons, Thomas(Feb 2020) Antigens: Carbohydrates II. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000500.pub2]