Other Proteins of the Classical Pathway

The isolation of C4 was described by Miiller-Eberhard and Biro (1963), Schreiber and Miiller-Eberhard (1974), Nagasawa et al. (1976), 

000) connected by disulfide bonds, and the molecular weight of intact C4 is 210,000 (Schreiber and Miiller-Eberhard, 1974). The three-chain structure is very unusual for plasma proteins, and Hall and Colten (1977) have suggested that it is synthesized as a single polypeptide chain. The NH2 terminals of the a, /8, and y chains are Asp, Lys, and Glu, respectively, and the NH2-terminal sequences have been partially determined (Bolotin et a/., 1977). 

A genetically determined structural polymorphism was detected in C4, and at least seven different patterns were reported (Rosenfeld et aL, 1969). The polymorphism of C4 was formed by varying combinations of three subtypes, C, A, and Ai (Rosenfeld et aL, 1969). A C4 structural gene was shown to be linked to the HLA gene complex on chromosome 6, as in the case of C2, C8, and factor B of the alternative pathway (Teisberg er /., 1976 Bitter-Suermann a/., 1977). 

Cls activates C4 by cleaving an X-Ala peptide bond (Nagasawa et al., 1976) on the a chain of C4, producing a small NH2-terminalfragment, C4a (molecular weight 8600) and a larger C4b portion (molecular weight 

On cleavage of C4 by Cls, C4b acquires two binding sites, a labile site which allows the C4b to attach itself to cell membranes and a stable site which enables cell-bound C4 to react with a C4b receptor on human erythrocytic and lymphocytic cells, producing immune adherence (Cooper, 1969 Bokisch and Sobel, 1974). The labile binding site is thermodynamically unstable and quickly loses its binding ability. Conse- 

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