A SYNTHETIC PEPTIDE FROM COMPLEMENT PROTEIN C9 BINDS TO CD59 AND ENHANCES LYSIS OF HUMAN ERYTHROCYTES BY C5B-9

The membrane glycoprotein CD59 protects host cells from homologous com plement attack by inhibiting the assembly of the membrane attack compl ex. CD59 binds to C8 and C9 in the nascent membrane attack complex and interferes with C9 membrane insertion and polymerization. We show her e that a synthetic peptide from the putative C9 hinge region, postulat ed to be involved in the rearrangement of C9 globular domains during m embrane insertion, binds specifically to CD59 and enhances lysis of hu man erythrocytes by the terminal complement C5b-9 complex. The peptide , C9H, caused a dose-dependent increase in the sensitivity of human er ythrocytes to C5b-9-mmediated lysis by interfering with the final C9 b inding and/or membrane insertion step. C9H exhibited species-specifici ty, since it had no activity against guinea pig C8 and C9 or on the pu tative functional homologues of CD59 in guinea pig erythrocytes. A dir ect association between CD59 and C9H was suggested by two different bi nding experiments: C9H inhibited the binding of I-125-labeled CD59 to immobilized C9, and C9H immobilized to microtiter plates bound purifie d CD59 and selectively recognized CD59 from extracts of detergent-solu bilized human erythrocyte membranes. These data indicate that the pept ide C9H corresponds to a region of the CD59 binding site of C9.