Complement Decay-Accelerating Factor (CD55)

Complement decay-accelerating factor, also known as CD55 or DAF, is 70 kDa glycoprotein that is encoded by the CD55 gene. The encoded protein is found on the membranes of vascular endothelial cells, peripheral blood cells, placenta, and many types of epithelial cells. DAF protein contains four complement control protein (CCP) domains with a single N-linked glycosylation site between CCP1 and CCP2, a heavily O-glycosylated membrane proximal domain, and a glycosylphosphatidylinositol (GPI) anchor which anchors the protein to phospholipids on the cell membrane. Without the anchor phospholipid, DAF can also exist in a soluble form and has been found in many body fluids including plasma, urine, tears, saliva, synovial and cerebrospinal fluids.

DAF plays a crucial role in protecting host cells from autologous complement attacks. It prevents the formation of C4b2a and C3bBb through binding to cell-associated C4b and C3b polypeptides, thereby suppressing amplification convertases of the complement cascade. It also inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases. Moreover, DAF is a receptor for some viruses such as several echoviruses and certain types of echo- and coxsackie B-viruses. Some pathogens such as HIV have been found to transfer GPI-anchored DAF into their cell membranes in a functionally active form.

DAF deficiencies are associated with several diseases including paroxysmal nocturnal haemoglobinuria, and autoimmune diseases. Recent studies reported DAF is involved in tumorigenesis and the DAF expression levels are increased in many types of malignant tumors.

Fig.1 Overview of complement activation by human anti-EGFR-IgG3 in the context of CD55 expression. (Rosner, 2014)

Reference

1. Rosner, T.; et al. Epidermal growth factor receptor targeting IgG3 triggers complement-mediated lysis of decay-accelerating factor expressing tumor cells through the alternative pathway amplification loop. Journal of Immunology. 2014, (193)3: 1485-1495.