The binding of human complement component C4 to antibody-antigen aggregates

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Abstract
The binding of human complement component C4 to antibody-antigen aggregates and the nature of the interaction were investigated. When antibody-antigen aggregates with optimal C.hivin.1 [activated C1] bound are incubated with C4, the C4 is rapidly cleaved to C4b, but only a small fraction (1-2%) is bound to the aggregates, the rest remaining in the fluid phase as inactive C4b. C4b and the antibody form a very stable complex, due probably to the formation of a covalent bond. On reduction of the C4b-IgG complex, the .beta. and .gamma. chains, but not the .alpha.'' chain, of C4b are released together with all the L chain, but only .apprx. 1/2 of the H chain of IgG. The reduced aggregates contain 2 main higher MW complexes, 1 shown by the use of radioactive components to contain IgG and C4b and probably therefore the .alpha.'' chain of C4b and the H chain of IgG, and the other only C4b and probably an .alpha.'' chain dimer. The aggregates with bound C.hivin.1 and C4b show maximal C3 convertase activity, in the presence of excess C2, when the .alpha.''-H chain component is in relatively highest amounts. When C4 is incubated with C.hivin.1s in the absence of aggregates, up to 15% of a C4b dimer is formed, which on reduction gives an .alpha.'' chain complex, probably a dimer. The apparent covalent interaction between C4b and IgG and between C4b and other C4b molecules cannot be inhibited by iodoacetamide and hence cannot be catalyzed by transglutaminase (factor XIII). The reaction is inhibited by cadaverine and putrescine and 14C-labeled putrescine is incorporated into C4, again by a strong, probably covalent, bond. A reactive group, possibly an acyl group, is generated when C4 is activated by C.hivin.1 and this reactive group can react with IgG, with another C4 molecule, or with water.