Abstract
During the mid-1980s, in vitro rosette formation between macrophages and sheep erythrocytes was reported; however, sialidase treatment on erythrocytes abolished the rosettes [1]. Rosette formation is based on sialic acid-binding receptors expressed by macrophages. Later, these receptors were identified to be sialoadhesin that binds to sialic acids as ligands [2]. The SA-recognizing property of the innate immune system of vertebrates led to the discovery of SA-bearing glycans as the ligands for lectins. The binding of SA ligands to Siglecs with immune inhibitory properties leads to suppressed immune functions. The SA-to-Siglec recognition implicates immune activation to limit self-recognition and to destroy the defense mechanism in hosts. Siglecs attenuate ‘self’-inflammatory triggers called DAMPs. During the early 1990s, the first sialyl carbohydrate-binding receptor protein called Siglecs was discovered, for example, Siglec-2 (or CD22) present on B cells. Siglec-1, known as sialoadhesin present on macrophage surfaces, was found. The Ig-like domains of such lectins are different from those of other known C-type lectins or Ca2+-dependent lectins. Among them, I-type lectins are named I-type because they belong to the varied immunoglobulin superfamily of proteins. As I-type lectins share similar characteristics with the immunoglobulin superfamily of proteins, they contain Ig folds, which consist of antiparallel β-sheets. I-type lectins can be broken down into many different regions: V-set, C1 and C2 sets, and ITIM and ITIM-like domains. The V-set domain is the primary site of ligand binding and recognition. The C1 and C2 sets act as spacers and are believed to control the entire length of lectins. ITIM and ITIM-like domains (in some cases, ITAM domain) are essentially tyrosine-based signaling motifs that inhibit (or, in the case of the ITAM domain, activate) downstream signaling and thereby modulate cell activities. More than 16 I-type lectins, such as Siglecs, recognize diverse sialoglycans by immune cells. Even among I-type lectins, there are many different subtypes and the best characterized subtype is called Siglecs. Siglecs are SA-binding lectins and they are the most well-studied I-type lectins. Like any other lectins, Siglecs are composed of many different domains, namely, the V-set, C1 and C2 sets, and mostly the ITIM domains.
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Kim, CH. (2022). Sialic Acid-Binding Ig-Like Lectins (Siglecs). In: Glycobiology of Innate Immunology. Springer, Singapore. https://doi.org/10.1007/978-981-16-9081-5_7
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