Complement C2 Receptor Inhibitor Trispanning: A Novel Human Complement Inhibitory Receptor

• Published in: The Journal of immunology (1950) Vol. 174; no. 1; pp. 356 - 366
• Main Authors: Inal, Jameel M, Hui, Kwok-Min, Miot, Sylvie, Lange, Sigrun, Ramirez, Marcel Ivan, Schneider, Brigitte, Krueger, Gerhard, Schifferli, Jurg-A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.01.2005
• Subjects: Amino Acid Sequence; Animals; Antigens, Helminth - chemistry; Antigens, Helminth - genetics; Blood Cells - metabolism; Blotting, Southern; Blotting, Western; Cell Line; Complement C2 - metabolism; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Helminth Proteins - chemistry; Helminth Proteins - genetics; Humans; Immunohistochemistry; Molecular Sequence Data; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - genetics; Sequence Homology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.1.356

The complement system presents a powerful defense against infection and is tightly regulated to prevent damage to self by functionally equivalent soluble and membrane regulators. We describe complement C2 receptor inhibitor trispanning (CRIT), a novel human complement regulatory receptor, expressed on hemopoietic cells and a wide range of tissues throughout the body. CRIT is present in human parasites through horizontal transmission. Serum complement component C2 binds to the N-terminal extracellular domain 1 of CRIT, which, in peptide form, blocks C3 convertase formation and complement-mediated inflammation. Unlike C1 inhibitor, which inhibits the cleavage of C4 and C2, CRIT only blocks C2 cleavage but, in so doing, shares with C1 inhibitor the same functional effect, of preventing classical pathway C3 convertase formation. Ab blockage of cellular CRIT reduces inhibition of cytolysis, indicating that CRIT is a novel complement regulator protecting autologous cells.