CD Antigens

Key Biological Properties: CD33 is a glycosylated transmembrane protein that plays a role in cell-cell interactions and maintaining immune cells in a resting state . It contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its intracellular portion, which are involved in the inhibition of cellular activity .

Expression Patterns and Tissue Distribution: CD33 is predominantly expressed on myeloid cells, including monocytes, granulocytes, and macrophages . It is also found in the spleen, bone marrow, and blood . Additionally, CD33 expression has been observed in some lymphoid cells .

Primary Biological Functions: CD33 functions as an inhibitory receptor that downregulates cell activation upon phosphorylation of its ITIM sequence . It plays a crucial role in immune responses by inhibiting phagocytosis and regulating the production of inflammatory cytokines .

Role in Immune Responses and Pathogen Recognition: CD33 is involved in the recognition of sialic acid-modified proteins or lipids, which are common on the surface of pathogens . This recognition helps in the regulation of immune responses and the prevention of excessive inflammation .

Mechanisms with Other Molecules and Cells: Upon binding to sialic acid residues, the ITIMs of CD33 are phosphorylated, creating docking sites for Src homology 2 (SH2) domain-containing proteins such as SHP-1 and SHP-2 phosphatases . This recruitment leads to the inhibition of downstream signaling cascades, ultimately reducing cellular activation .

Binding Partners and Downstream Signaling Cascades: CD33 interacts with various sialic acid-containing ligands, including glycoproteins and glycolipids . The binding of these ligands triggers the phosphorylation of ITIMs and the recruitment of SHP-1 and SHP-2, which inhibit signaling pathways involved in cell activation .

Regulatory Mechanisms Controlling Expression and Activity: The expression and activity of CD33 are regulated by various mechanisms, including transcriptional regulation and post-translational modifications . Suppressor of cytokine signaling 3 (SOCS3) can bind to the phosphorylated ITIM of CD33, leading to its accelerated proteasomal degradation .

Transcriptional Regulation and Post-Translational Modifications: CD33 expression is influenced by cytokines and other signaling molecules that modulate its transcription . Post-translational modifications, such as phosphorylation, play a critical role in regulating CD33 activity and its interactions with other proteins .

Biomedical Research: CD33 is widely studied in the context of hematological malignancies, particularly acute myeloid leukemia (AML) . It serves as a marker for myeloid cells and is used to study myeloid differentiation and immune regulation .

Diagnostic Tools: CD33 is utilized in diagnostic tools such as flow cytometry and immunohistochemistry to identify and characterize myeloid cells in various diseases .

Therapeutic Strategies: CD33 is a target for immunotherapy in AML, with therapies such as antibody-drug conjugates and chimeric antigen receptor (CAR) T cells being developed to target CD33-expressing cells . These therapies aim to selectively eliminate malignant cells while sparing normal cells .

Role Throughout the Life Cycle: CD33 plays a role in the regulation of immune responses throughout the life cycle, from development to aging . It is involved in maintaining immune homeostasis and preventing excessive inflammation . Dysregulation of CD33 expression or function has been implicated in various diseases, including hematological malignancies and neurodegenerative disorders .