Distinct ligand binding properties of Mac-2-binding protein and mousephilin C-associated protein

Human Mac-2-binding protein (Mac-2-BP) is a secreted glycoprotein that is w idely expressed. It binds to the human macrophage-associated lectin Mac-2 a nd has been suggested to have a role in host defence. Mouse cyclophilin C-a ssociated protein (mCyCAP) is also a secreted glycoprotein that binds with high affinity to cyclophilin C in the absence of the immunosuppresive drug cyclosporin A. The two proteins share a similar domain structure and consid erable sequence identity, including a highly conserved scavenger receptor c ysteine-rich domain, and both of them exert their function within the immun e system. To elucidate whether these molecules are also functional homologu es, we compared their ligand binding properties using cell lines which expr ess Mac-2-BP or mCyCAP as well as transfected cell lines stably expressing mCyCAP or a mutant version lacking the scavenger domain. These experiments show that Mac-2-BP is unable to bind to either human or mouse cyclophilin C and that mCyCAP cannot bind to Mac-2. The scavenger domain is not required for the interaction between mCyCAP and cyclophilin C. We conclude that the se proteins may be part of a larger family of proteins of immunological imp ortance in which closer functional homologues might exists.