MECHANISM OF ANTIBODY FORMATION 139 



by pepsin-treated antitoxin has been suggested by other investigators 

 to be due to the hmited amount of antigen that could be injected. 

 Coghill, et al. (1940) reported that diphtheria antitoxin which had 

 been despeciated by treatment with taka-diastase did not kill guinea 

 pigs sensitized passively to normal horse serum, and only a few 

 despeciated sera gave any anaphylactic reaction at all. The guinea pigs 

 sensitized with serum treated with taka-diastase could be shocked but 

 only with large doses of the same antigen. Kass, Scherago and Weaver 

 (1942) reported that ileum segments from guinea pig sensitized 

 passively to normal horse pseudo-globulin failed to respond to sera 

 digested vdth enzyme. Christensen and Kerrick (1948) confirmed this 

 observation and found that guinea pigs sensitized to pepsin-treated 

 serum will react when tested with the same antigen, but also show 

 that this cannot be due to the remaining horse serum specificity, 

 because pepsin-treated serum is significantly more effective in eliciting 

 anaphylactic shock in guinea pigs sensitized to pepsin-treated serum 

 than in guinea pigs sensitized to normal horse serum. They concluded 

 that "pepsin-treated antitoxin not only has retained some of its original 

 horse serum specificity, but in addition as a result of the process of 

 purification, has acquired a new antigenic specificity." In this study 

 there is not a detailed description of the purification of the pepsin- 

 treated antitoxin, and, therefore, the presence of normal serum com- 

 ponents is not excluded. Neither is there any evidence to show that 

 treatment of normal antitoxic globulins with pepsin accords new 

 specificity to these serum components. The new antigenicity which 

 these investigators have observed does not, therefore, appear to be 

 due to peptic digestion, nor to the process of purification, but rather 

 to the nature of the original antitoxin molecule. 



h. Crystalline Diphtheria Antitoxin Antigenically Distinct from 

 Normal Serum Components. The inability of the previous investi- 

 gators to differentiate the antigenic specificity of the antibody from that 

 of normal globulin may perhaps be attributed to the fact that even the 

 antibodies precipitated with their homologous antigens contain as 

 integral portions of their molecules components indistinguishable from 

 normal serum globulins. It has been shown by Parfentjev (1936, 

 1938), Pope (1938, 1939), and others that treatment of diphtheria 

 antitoxin with pepsin under certain conditions splits the antitoxin 

 into an active and an inactive portion. This observation has been 



