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Review
. 2023 Nov 21;5(4):e00035.
doi: 10.1097/IN9.0000000000000035. eCollection 2023 Oct.

N-linked glycans: an underappreciated key determinant of T cell development, activation, and function

Mahmoud Abdelbary  1 , Jeffrey C Nolz  1   2   3
Affiliations
Review

N-linked glycans: an underappreciated key determinant of T cell development, activation, and function

Mahmoud Abdelbary et al. Immunometabolism (Cobham). .

Abstract

N-linked glycosylation is a post-translational modification that results in the decoration of newly synthesized proteins with diverse types of oligosaccharides that originate from the amide group of the amino acid asparagine. The sequential and collective action of multiple glycosidases and glycosyltransferases are responsible for determining the overall size, composition, and location of N-linked glycans that become covalently linked to an asparagine during and after protein translation. A growing body of evidence supports the critical role of N-linked glycan synthesis in regulating many features of T cell biology, including thymocyte development and tolerance, as well as T cell activation and differentiation. Here, we provide an overview of how specific glycosidases and glycosyltransferases contribute to the generation of different types of N-linked glycans and how these post-translational modifications ultimately regulate multiple facets of T cell biology.

Keywords: N-linked glycans; T cells; glycobiology; glycosylation; immune responses.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1.
Figure 1.
Enzymatic synthesis of complex N-linked glycans occurs in a sequential fashion through the action of specific glycosidases and glycosyltransferases. Trimming of terminal mannose residues through the action of α-mannosidase-I is required for hybrid N-linked glycan synthesis by the addition of GlcNAc by Mgat1. Further trimming of mannose by α-mannosidase-II and addition of GlcNAc by Mgat2 results in the precursor for the synthesis of complex N-linked glycans. The collective action of additional glycosyltransferases (Mgat5, Fut8, ST6Gal-I, etc) determines the extent of branching and complexity of the final N-linked glycan chain. The majority of complex N-linked glycans are decorated on one or more branches with extended repeats of N-acetyllactosamine, composed of β1,3-Gal-β1,4-GlcNAc, which are terminated following the capping of these repeats with an N-acetylneuraminic acid (Neu5Ac; Sialic acid) by ST6Gal-I. Fut8, fucosyltransferase 8; Man1a1, mannosidase-I; Man2a2, mannosidase-II; Mgat1, N-acetylglucosaminyltransferase-I; Mgat2, N-acetylglucosaminyltransferase-II; Mgat5, N-acetylglucosaminyltransferase-V; ST6Gal-I, β-Galactoside α2,6-sialyltransferase-I; UDP-GlcNAc, uridine diphosphate-GlcNAc.
Figure 2.
Figure 2.
Three major types of N-linked glycans and their influence on T cell biology. In general, high-mannose, N-linked glycans are typically detrimental to T cells and severely impair thymocyte maturation leading to the development of various autoimmune diseases. Hybrid N-linked glycans containing terminal mannoses, but carrying a single branch are sufficient for normal development of thymocytes. Complex N-linked glycans can be highly diverse and regulate many aspects of T cell function and differentiation within the periphery to guard against hyperactivity, inflammation and autoimmunity.
Figure 3.
Figure 3.
Core fucosylation of N-linked glycans regulates multiple facets of T cell biology. Fucosyltransferase 8 (Fut8) catalyzes the addition of an a1,6 linkage fucose to the innermost N-acetylglucosamine residue of N-linked glycans, a process known as core fucosylation. Core fucosylation of N-linked glycans influences T cell activity and function through a variety of known and proposed mechanisms.
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References

    1. Trombetta ES, Helenius A. Lectins as chaperones in glycoprotein folding. Curr Opin Struct Biol. 1998;8(5):587–92. - PubMed
    1. Saito Y, Ihara Y, Leach MR, et al. . Calreticulin functions in vitro as a molecular chaperone for both glycosylated and non-glycosylated proteins. EMBO J. 1999;18(23):6718–29. - PMC - PubMed
    1. Wormald MR, Dwek RA. Glycoproteins: glycan presentation and protein-fold stability. Structure. 1999;7(7):R155–60. - PubMed
    1. Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell. 2006;126(5):855–67. - PubMed
    1. Schachter H. The joys of HexNAc. The synthesis and function of N- and O-glycan branches. Glycoconj J. 2000;17(7–9):465–83. - PubMed