Co-operative interaction of subcomponents of the first component of complement with IgG: a functional defect of dimeric Facb from rabbit IgG.
By following dissociation kinetics of radiolabelled C1q from rabbit IgG antibody-sensitized sheep red blood cells (SRBC) before and after its incorporation in the C1 complex, it was demonstrated that the binding stability is markedly enhanced by the presence of the C1r2-C1s2 subunit of C1 which by itself exhibits no significant binding capacity to immune complexes. The dissociation of C1q was decreased by up to 95%, the extent of decrease being pronounced as the cell surface IgG antibody density increased. However, such a stabilizing effect of C1r2-C1s2 was largely abolished when SRBC sensitized with the dimeric fragment F(acb)2 lacking C gamma 3 was used as the C1 binder, whereas the dissociation rate of uncomplexed C1q from F(acb)2-sensitized cells was similar to that from whole IgG-sensitized cells. It was also shown that, although the C1r2-C1s2 subunit is dissociated selectively from C1 bound to either IgG- or F(acb)2-sensitized cells in the presence of EDTA, it is held on much longer by the former cells than the latter cells. These results were taken to indicate that, although the C1 fixation by immune complexes of IgG is undertaken primarily by the interaction between C1q and the C gamma 2 domain, it is also strengthened by the secondary interaction between the C1r2-C1s2 subunit of C1 and the C gamma 3 domain or a structure which is dependent on the pair of C gamma 3 domains.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D003166:Complement Activating Enzymes / Q000378:metabolism; D003172:Complement C1 / Q000378:metabolism*; D015922:Complement C1q; D015923:Complement C1r; D003173:Complement C1s; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006461:Hemolysis; D006863:Hydrogen-Ion Concentration; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism*; D008956:Models, Chemical; D011817:Rabbits
D000936:Antigen-Antibody Complex; D003172:Complement C1; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; C041323:immunoglobulin Facb fragment; D015922:Complement C1q; D004492:Edetic Acid; D003166:Complement Activating Enzymes; D015923:Complement C1r; D003173:Complement C1s