Treatment of human IgG with cyanogen bromide in 0.05 M HCl under specified conditions resulted in the cleavage of about half of its methionyl peptide bonds. A major fragment of about 5S was isolated from the reaction mixture by gel filtration in quantitative yield. The CNBr fragment reacted fully with goat antiserum against human light chain, but its reaction with anti-heavy chain was markedly decreased. The treatment with CNBr caused a drastic decrease in the following biological activities of IgG: complement fixing, skin binding, reaction with antiglobulin factors, and reaction with specific anti-Gm(12) serum. On the other hand, the reaction with serum of anti-Gm(1) or anti-Gm(4) specificity was not impaired and antibody activity, namely antistreptolysin and isohemagglutinin, was retained after the treatment with CNBr.
It is concluded that the CNBr cleaves preferentially the methionyl bonds in the Fc portion of IgG, and that the major fragment obtained, denoted F(ab'')2, has still the combining properties of a divalent antibody. The possible therapeutic uses of F(ab'')2 are discussed.