CD33related

CD33related refers to the CD33-related Siglec subfamily, a subset of sialic acid–binding immunoglobulin-like lectins (Siglecs) that are more divergent and rapidly evolving compared with the conserved Siglecs. In humans, these receptors are encoded largely on chromosome 19 and share extracellular immunoglobulin-like domains, a single-pass transmembrane region, and cytoplasmic signaling motifs that commonly include ITIMs. They recognize sialylated glycans, with binding specificities that vary among family members.

Expression patterns and function vary among the CD33-related Siglecs, but they are predominantly found on myeloid lineage cells and, in some cases, on other leukocytes. Functionally, many CD33-related Siglecs dampen immune cell activation when engaged by their ligands, contributing to self-tolerance and the control of inflammatory responses. Signaling often involves recruitment of phosphatases such as SHP-1 or SHP-2 via ITIMs, leading to attenuation of activation signals.

Biological and clinical significance is linked to immune regulation and disease. Engagement by tumor- or microbe-derived sialylated ligands can promote immune evasion, and altered expression of CD33-related Siglecs has been observed in various hematologic and inflammatory conditions. The best-known member is CD33 (Siglec-3), a therapeutic target in acute myeloid leukemia, where antibody-based therapies and antibody-drug conjugates have been explored in clinical settings.

Nomenclature-wise, the CD33-related group is distinguished from conserved Siglecs such as Siglec-1, Siglec-2, and Siglec-4. The CD33-related Siglecs exhibit greater species-specific variation, which shapes their study in human immunology and disease contexts.