176 CHEMIHTRY OF THE IMMJ-XITY REACTIOXS 



specificity: There exist two sorts of specificity in each protein 

 molecule; one of these is easily altered by simple physical measures, 

 e. g., heat, cold, partial coagulation, etc., without essentially chang- 

 ing the chemical composition of the protein. AVheu so altered the 

 antigenic properties of the protein are likewise altered, in that the 

 antibody it engenders differs somewhat in the scope of its reactivity, 

 from the antibody engendered by the original unaltered protein; but 

 the alteration does not affect the species characteristics of the antigen. 

 Thus, a heated antigen may engender ]-)recipitins that will react with 

 this heated antigen, but not with similar heated proteins from other 

 species of animals, while the antibodies engendered by the same but 

 unheated antigen will not react with the heated protein. 



The other sort of specificity is not so easily affected, only marked 

 chemical alterations of the antigen modifying it, and this concerns the 

 species characteristics of the antigen. This fundamental species speci- 

 ficity seems to be closely related to the aromatic radicals of the protein 

 antigen, for it is affected by introducing into the protein molecules 

 substances which are known to combine with the benzene ring, 

 e. g., iodin, diazo and nitro groups. Proteins thus chemically altered 

 will act as proteins foreign to animals of the species from which they 

 are derived, and the antigens they develop are devoid of species 

 specificity, although quite specific for proteins like themselves ; e. g., a 

 nitro-protein made by treating rabbit serum protein with nitric acid, 

 will, if injected into even the same rabbit, cause the formation of 

 antibodies which will react with this same nitro-protein, and also 

 with nitro-proteins derived from entirely different species or even 

 from plants, — but it reacts only with nitro-proteins. It is also possi- 

 ble to cause chemical modifications analogous to the physical modi- 

 fications previously mentioned, which change only the scope of 

 specificity of the antigen without altering its specificity for species. 

 A])preciating that the number of different aromatic radicals in the 

 protein molecule is not sufficient to account for the innumerable 

 manifestations of specificity. Pick interprets the significance of these 

 aromatic radicals as that of a central complex about which are the 

 g7-ou])iiigs wliicli determine species s])ecificity.''-''^ Tt is not merely the 

 number and proportion of amino-acid radicals in the jn'otein molecule 

 which determine its specificity, but, more important because present- 

 ing greater possibilities for variations, the arrangement of these 

 radicals in the molecule. Contemplating the possible number of 



infj substances imist liarinoiii/.o, just as tlio \ilpratioii of one tuniuir fork starts 

 vibrations in anotiier fork only when Die two are in liarinonv. or as electroinair- 

 netio waves incite resonance phenomena (see Zeit. f. Iinmunitiit., 1911 (0), 246 

 and 779). 



■«2a Landsteiner and Prasek (Zoit. Innnunitiit.. 1913 (20). 211 ), lic)W(>ver, state 

 that alteration of proteins by simply treatin<f tliem with acid alcolio! also causes 

 them to lose their species specificity, and this witliout aiiy substitution in the 

 aromatic radicals of the proteins. This observation throws doub* on the hypothe- 

 sis of Pick that tiic aromatic radicals ai'c the essential center of sjx'cics specificity. 



