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Review
. 2001 Jun;103(2):137-45.
doi: 10.1046/j.0019-2805.2001.01241.x.

Siglecs in the immune system

P R Crocker  1 , A Varki
Affiliations
Review

Siglecs in the immune system

P R Crocker et al. Immunology. 2001 Jun.
No abstract available

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Figures

Figure 1
Figure 1
Structural features of Siglecs. (a) Siglecs are type I membrane proteins with an extracellular region containing a sialic acid binding V-set Ig-like domain at the N-terminus and 1–16 C2-set Ig-like domains. The cytoplasmic tails of all Siglecs apart from sialoadhesin have one or more tyrosine residues within potential signalling motifs. A crystal structure of the sialoadhesin N-terminal domain complexed to 3′-sialyllactose revealed some key features of sialic acid recognition by Siglecs, including the presence of an essential arginine (Arg97) on the F strand (conserved in the other Siglecs) which forms a salt bridge with the carboxylate of sialic acid (b). The V-set and adjacent C2-set domains of Siglecs contain an unusual arrangement of conserved cysteines that give rise to an intrasheet disulphide (rather than the more usual intersheet disulphide) within the V-set domain and a disulphide between the domains. The conserved intrasheet disulphide in sialoadhesin results in widening of the Ig β-sandwich and exposure of two tryptophans (Trp2 and Trp106) on the A and G strands that form hydrophobic contacts with the N-acetyl and glycerol side groups of NeuAc, respectively (see for further details).
Figure 2
Figure 2
Diagram illustrating how the interaction of Siglecs with cells or sialylated pathogens could be affected by cis interactions with sialylated glycoconjugates. (a) (i) Some Siglecs such as sialoadhesin appear to be unmasked and able to mediate cell–cell interactions constitutively whereas (ii) the majority of Siglecs appear to be naturally masked due to cis interactions with adjacent sialic acids. Cis interactions may be important for signalling functions; for example CD22 is closely associated with the B-cell receptor complex and provides inhibitory signals that raise B-cell activation thresholds. (iii) Unmasking of Siglecs can occur in some cases by cellular activation or by exposure to sialidases. The unmasked Siglec may now be capable of stronger interactions with ligands on other cells. This could result in increased cellular interactions and/or signalling. (iv) In another scenario, a virally infected cell expressing a viral sialidase (neuraminidase) on the cell surface would result in loss of Siglec ligands and reduced interactions with unmasked Siglecs on cells of the innate immune system. In this situation, unmasking of Siglecs could also occur by close cell–cell contact with the virally infected cell. (b) Some pathogens can express sialylated glycoconjugates (see text for details) which may interact with Siglecs. In the case of sialoadhesin, this may lead to increased uptake of pathogens by macrophages and therefore be detrimental to the pathogen. In the case of CD22- and CD33-related Siglecs, interactions with sialylated pathogens may lead to subversion of the normal signalling functions of Siglecs (e.g. reduced activation) which could result in increased pathogen survival.
See this image and copyright information in PMC

References

    1. Crocker PR, Clark EA, Filbin M, et al. Siglecs: a family of sialic-acid binding lectins [letter] Glycobiology. 1998;8:v. - PubMed
    1. Powell LD, Varki A. I-type lectins. J Biol Chem. 1995;270:14243–6. - PubMed
    1. May AP, Robinson RC, Vinson M, Crocker PR, Jones EY. Crystal structure of the N-terminal domain of sialoadhesin in complex with 3′ sialyllactose at 1.85 Å resolution. Mol Cell. 1998;1:719–28. - PubMed
    1. Crocker PR, Gordon S. Properties and distribution of a lectin-like hemagglutinin differentially expressed by murine stromal tissue macrophages. J Exp Med. 1986;164:1862–75. - PMC - PubMed
    1. Stamenkovic I, Seed B. The B-cell antigen CD22 mediates monocyte and erythrocyte adhesion. Nature. 1990;345:74–7. - PubMed

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