PURIFICATION AND CHARACTERIZATION OF THE PIG ANALOG OF HUMAN MEMBRANECOFACTOR PROTEIN (CD46 MCP)/

A panel of mAbs were raised against pig lymphocytes. Seven mAbs immuno precipitated a 50- to 60-kDa membrane-bound protein. This protein, ter med JM4C8-Ag, was expressed on a wide variety of cells, including all circulating cells and cells of fibroblast, epithelial, and endothelial origin. The JM4C8-Ag was transmembrane-anchored and glycosylated. One of the Abs was used in immunoaffinity chromatography to isolate JM4C8 -Ag from erythrocyte membranes. N-terminal amino acid analysis through the first 28 residues showed a 43% homology with the human complement regulatory molecule membrane cofactor protein (MCP; CD46). The purifi ed protein had cofactor activity for factor I-mediated cleavage of hum an and pig C3b, confirming its identity as the pig analogue of human M CP. The purified protein also strongly inhibited lysis of rabbit eryth rocytes by human and pig complement after activation of the classical or alternative pathway. This is the first report of a nonprimate analo gue of MCP, The presence of a resident MCP on pig cells capable of act ing as a cofactor in the control of human complement activation has co nsequences for the use of pig organs in xenotransplantation.