THE 7-SPAN TRANSMEMBRANE RECEPTOR CD97 HAS A CELLULAR LIGAND (CD55, DAF)

CD97 is an activation-induced antigen on leukocytes with a seven-span transmembrane (7-TM) region homologous to the secretin receptor superf amily. However, in contrast to this group of peptide hormone receptors , CD97 has an extended extracellular region with three EGF domains at the NH2 terminus, two of them with a calcium binding site. By demonstr ating that lymphocytes and erythrocytes specifically adhere to CD97-tr ansfected COS cells we here show that CD97 in parallel with its molecu lar evolution has acquired the ability to bind cellular ligands. A mAb selected on its capacity to block the adhesion between CD97 transfect ants and red cells was found to be directed to the NH2-terminal short consensus repeat (SCR) of decay accelerating factor (DAF, CD55), a reg ulatory protein of the complement cascade. The specificity of the inte raction of CD97 with CD55 was established by the observation that eryt hrocytes that lack CD55, obtained from patients with paroxysmal noctur nal hemoglobinuria (PNH) or the CD55(-) phenotype Inab, failed to adhe re to CD97 transfectants. This is the first demonstration of a cellula r ligand for a 7-TM receptor.