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  • Review Article
  • Published:

Mammalian glycosylation in immunity

Nature Reviews Immunology volume 8, pages 874–887 (2008)Cite this article

This article has been updated

Key Points

  • Various types of mammalian extracellular glycan are produced in the secretory pathway. This Review covers the enzymatic synthesis of glycans and the mechanisms by which cellular glycans are regulated.

  • The basic framework by which glycan structures can control molecular interactions is provided, with examples of glycoprotein conformation, glycoprotein maturation and the binding of glycan receptors known as lectins.

  • The roles of mammalian glycans in the innate and adaptive immune systems are reviewed, as well as examples of glycan-dependent functions in the ontogeny of various immune cell types.

  • This Review encompasses a discussion and tabulation of mammalian glycan linkages, the enzymes that produce them and their cognate recognition molecules that include lectin receptors, in the context of the immune system.

  • The role of mammalian glycosylation in controlling the activation of intracellular phosphorylation and signal-transduction pathways is detailed. We review the molecular mechanisms that explain how the glycosylation of cell-surface molecules can govern the assembly and function of glycoprotein signalling complexes.

  • Important outstanding questions and unexplored areas are discussed in the context of current methodologies and potential future technologies. We discuss examples of how blocking single enzymes in mammalian glycosylation can either elicit or prevent diseases of the immune system.

Abstract

Glycosylation produces a diverse and abundant repertoire of glycans, which are collectively known as the glycome. Glycans are one of the four fundamental macromolecular components of all cells, and are highly regulated in the immune system. Their diversity reflects their multiple biological functions that encompass ligands for proteinaceous receptors known as lectins. Since the discovery that selectins and their glycan ligands are important for the regulation of leukocyte trafficking, it has been shown that additional features of the vertebrate immune system are also controlled by endogenous cellular glycosylation. This Review focuses on the emerging immunological roles of the mammalian glycome.

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Figure 1: The types of mammalian glycan.
Figure 2: Basic mechanisms of glycan function in the immune system.
Figure 3: Glycans in T-cell-receptor activation.
Figure 4: Glycans in B-cell-receptor activation.

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  • 15 October 2008

    In the version of this article initially published online, there was an unnecessary "of" in the abstract. This error has been corrected for the print, HTML and PDF versions of the article.

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Acknowledgements

We apologize to the colleagues and researchers who have made contributions that were not referenced owing to space limitations. J.D.M. is supported by the Howard Hughes Medical Institute and grants from the National Institutes of Health, USA (HL57345, HL78784 and GM62116).

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    Jamey D. Marth & Prabhjit K. Grewal

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Glycome

The biological repertoire of glycan structures.

Experimental autoimmune encephalomyelitis

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A type of lymphoma that is characterized by the presence of Reed–Sternberg cells (derived from B cells) and that spreads between the lymph nodes.

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Marth, J., Grewal, P. Mammalian glycosylation in immunity. Nat Rev Immunol 8, 874–887 (2008). https://doi.org/10.1038/nri2417

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