QUANTITATIVE-ANALYSIS C4AB AND C4BB BINDING TO THE C3B C4B RECEPTOR (CR-1, CD35)/

Complement-dependent clearance of immune complexes in humans is depend ent on the activation and binding of the early components of the class ical complement cascade. This prevents immune complex precipitation an d promotes binding of the complexes by the C4b/C3b complement receptor CR1 (CD35) found on erythrocytes, The fourth component of human compl ement is encoded by two closely Linked genes within the MMC. These gen es give rise to the isotypic forms C4A and C4B, and recent studies sug gest that CRI binds activated C4A (C4Ab) to a greater extent than acti vated C4B (C4Bb). To study this difference in a more quantitative way the binding reactions between CR1 and C4Ab- and C4Bb-coated immune com plexes and between CRI and soluble dimers of C4Ab (C4Ab(2)) and C4Bb ( C4Bb(2)) were analysed using the native receptor on human erythrocytes . The binding reaction between immune complexes with equivalent amount s of covalently bound C4Ab or C4Bb and erythrocyte CR1 showed a two-fo ld higher binding of complexes coated with C4A. Furthermore, erythrocy te CR1 bound C4Ab(2) with an apparent four-fold higher affinity (K-d a pproximate to 1.4x10(-7)M) than C4Bb(2) (K-d approximate to 4.8x10(-7) M), indicating a preferential binding of CR1 for C4A.