Complement component C8 plays a key role in the production of membrane damage by the complement system and it has a three-chain structure organized in two subunits,C8α-γ and C8β, which are held together by noncovalent bonds. The binding site for both the cell-bound and the fluid phase trimolecular complex C567 is situated on the β-chain. The two subunits can be separated by gel filtration in the presence of sodium dodecyl sulfate (SDS) and urea and then recombined to form hemolytically active C8.
Whereas cells which have reacted with seven components of complement (C1-C7) are apparently intact with respect to membrane function, these cells undergo lysis after reaction with complement C8. Cytolysis induced by C8 is independent of complement component C9 and in absence of C9 proceeds at a slow rate, which, however, is greatly accelerated upon addition of the terminal component. Accordingly, C8 may be regarded as that protein of complement which is directly responsible for production of complement dependent membrane damage.
The serum from some patients with complement C8 deficiency does not react with specific antiserum to human complement C8 to produce a precipitin line in immunodiffusion analysis. These sera are thought to completely lack the C8 molecule. Other patients owe their complement C8 deficiency to a dysfunctional C8 molecule that cross-reacts antigenically with C8 in the serum of normal individuals. Analysis of these dysfunctional C8 molecules has established that they lack the C8β-chain. Complement C8 deficiency due to the selective absence of the α-γ-subunit has not been recognized previously.
1. Manni J A, et al. (1969). The eighth component of human complement (C8): isolation, characterization, and hemolytic efficiency. The Journal of experimental medicine, 130(5), 1145-1160.
2. Tedesco F, et al. (1983). Two types of dysfunctional eighth component of complement (C8) molecules in C8 deficiency in man. Reconstitution of normal C8 from the mixture of two abnormal C8 molecules. Journal of Clinical Investigation, 71(2), 183.
3. Klob W P, et al. (1976). The membrane attack mechanism of complement: the three polypeptide chain structure of the eigth component (C8). The Journal of experimental medicine, 143(5), 1131-1139.