What Are CD33-Related Siglecs?

On the surface of myeloid progenitor cells, monocytes, macrophages, and microglia, CD33 Siglec (Siglec-3) is expressed. In contrast to conserved Siglecs, CD33 Siglec and CD33-related Siglecs appear to have developed fast through a variety of pathways, leading to significant changes in CD33-related Siglecs libraries in mammalian species.

Most cytosolic immunoreceptor tyrosine-based inhibitory motifs (ITIM) are present in human Siglecs. However, some Siglecs carry some basic amino acids that can detect molecules encoding tyrosine-based activation motifs (ITAMs) for signaling activation even though they lack intracellular domains. CD33 has a V Ig-like domain, a C2 Ig-like domain, a transmembrane domain, and a cytoplasmic tail with two conserved. CD33 is the only Siglec with a peroxisome targeting sequence in the cytoplasmic tail.

CD BioGlyco has established a Microarray Platform and offers Sialic Acid Microarray and Lectin Microarray Assay for customers to study CD33-related Siglecs.

Fig.1 Structure of the immune D33. (PDB)

The Family of CD33-Related Siglecs

In the human sialic-acid binding Siglec family, there are 10 CD33-related members: CD33 (Siglec-3), Siglec-5~11, Siglec-14, and Siglec-16. Siglec-13 had been deleted from CD33-related members. Sialic Acid-Specific Lectin Analysis is a tool you can find in CD BioGlyco to help study functions of CD33-related Siglecs.

Fig.2 Schematic drawing of human and murine Siglec receptors. (Läubli & Varki, 2019)

Their Role in Biology

Myeloid progenitor cell marker CD33 has the potential to control cell proliferation and/or differentiation. Later stages of hematopoiesis seem to see the expression of additional CD33-related Siglecs. Siglecs that are related to CD33 is also crucial for controlling leukocyte behavior because they promote the release of pro-inflammatory cytokines and suppress cell activation, proliferation, and death. Based on this, more and more Siglec Related Therapies are studied and applied. CD BioGlyco provides Targeting Carbohydrate-Lectin Interactions, Targeting Carbohydrates of Pathogens, and other Custom Glycosylation Services for customers to study CD33-related therapies.

• Siglec-3: CD33 is a target of antagonistic monoclonal antibody-based (mAb) and chimeric antigen receptor (CAR) T-cell immunotherapy, especially in adults and children with acute myeloid leukemia (AML).
• Siglec-5 and Siglec-14 Pairs: Siglec-5 and Siglec-14 are both highly homologous, usually expressed together, and recognize similar sialylation ligands. Siglec-5 carries an inhibitory ITIM motif to counterbalance the activation of Siglec-14.
• Siglec-6: It is an immunosuppressive CD33-related Siglec that binds strongly to Sialylated Tn structures. But only Siglec-6 does not require a glycerol side chain for binding.
• Siglec-7: It is a natural killer (NK) cell inhibitory receptor with an ITIM motif. Siglec-7 has a very high affinity for α2, 8-linked di-sialic acid residues, and is found to have two sialic acid binding sites instead of one.
• Siglec-8: Siglec-8 antibodies have recently emerged as a target of allergen-induced inflammation and can be used to treat eosinophilic gastritis and eosinophilic duodenitis.
• Siglec-9: It is an MHC class I-independent inhibitory receptor that recognizes the self-associated molecular pattern of Sia (SIA-SAMP) and transacts Siglec-mediated leukocyte apoptosis. It inhibits cell-mediated tumor cell killing by binding to Siglec-7 and Siglec-9 receptors.
• Siglec-10: It is an inhibitory ITIM with a CD33-related Siglec receptor that is mainly present in NK cells, B cells, monocyte-derived dendritic cells, and antigen-activated CD4 + T cells to suppress immune counterreaction.
• Siglec-11 and Siglec-16 Pairs: The inhibitory Siglec-11 is paired with the activating Siglec-16 receptor and is expressed on macrophages/microglia in the central nervous system and on fibroblasts in the ovary. Siglec-11 has a cytoplasmic ITIM motif, but Siglec-16 does not have a signal motif.

Why Choose Us?

CD BioGlyco is particularly interested in Lectins-related research fields, and we have a strong platform to provide relevant technical support to our customers. If you are interested in our services please contact us, our excellent service team looks forward to receiving your inquiries.

Reference:

1. Läubli, H.; and Varki, A. Sialic acid–binding immunoglobulin-like lectins (siglecs) detect self-associated molecular patterns to regulate immune responses. Cellular and Molecular Life Sciences. 2019, 77(4): 593–605.