title: Quantitative analysis of C4Ab and C4Bb binding to the C3b/C4b receptor (CR1, CD35).
abstract: Complement-dependent clearance of immune complexes in humans is dependent on the activation and binding of the early components of the classical complement cascade. This prevents immune complex precipitation and promotes binding of the complexes by the C4b/C3b complement receptor CR1 (CD35) found on erythrocytes. The fourth component of human complement is encoded by two closely linked genes within the MHC. These genes give rise to the isotypic forms C4A and C4B, and recent studies suggest that CR1 binds activated C4A (C4Ab) to a greater extent than activated C4B (C4Bb). To study this difference in a more quantitative way the binding reactions between CR1 and C4Ab- and C4Bb-coated immune complexes and between CR1 and soluble dimers of C4Ab (C4Ab2) and C4Bb (C4Bb2) were analysed using the native receptor on human erythrocytes. The binding reaction between immune complexes with equivalent amounts of covalently bound C4Ab or C4Bb and erythrocyte CR1 showed a two-fold higher binding of complexes coated with C4A. Furthermore, erythrocyte CR1 bound C4Ab2 with an apparent four-fold higher affinity (Kd approximately 1.4 x 10(-7) M) than C4Bb2 (Kd approximately 4.8 x 10(-7) M), indicating a preferential binding of CR1 for C4A.
authors.affiliation: Department of Health Sciences, University of Wisconsin-Milwaukee, 53201, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Reilly
authors.forename: C
authors.initials: C
authors.lastname: Mold
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology; D015934:Complement C4a / Q000276:immunology / Q000378:metabolism*; D015935:Complement C4b / Q000276:immunology / Q000378:metabolism*; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011869:Radioligand Assay; D017463:Receptors, Complement 3b / Q000276:immunology / Q000378:metabolism*
chemical_list: D000936:Antigen-Antibody Complex; D017463:Receptors, Complement 3b; D015934:Complement C4a; D015935:Complement C4b