7i8 THE CHEMISTRY OF ANTIGENS 



DELIBERATE ATTEMPTS TO MODIFY THE ANTIGEN MOLECULE 



Light has been thrown upon the nature of antigens and upon their structure and 

 the properties necessary for their activity by experiments in which the antigen mole- 

 cule has been deliberately changed in a definite known way, and the eflfect of the 

 changes upon activity has been studied. Aside from observing the effect on activity 

 and specificity caused by coagulation, denaturation, and racemization, the chemical 

 composition of the molecule has been changed by introducing or changing atomic 

 groups, 



Obermayer and Pick^ introduced iodine, nitro-, and diazo-groups into the aro- 

 matic ring of amino acids in beef-serum proteins. These changed proteins completely 

 lost their species specificity as antigens, antisera produced with them reacting not 

 only with the homologous altered protein, but with other proteins such as horse 

 serum, egg white, and even rabbit serum into which the same chemical groups had 

 been introduced; for example, horse serum with nitroprotein gave an antiserum which 

 did not react with normal horse serum or with iodized horse serum, but reacted with 

 horse serum containing nitroprotein and with other sera containing nitroprotein. 

 These results influenced Obermayer and Pick to conclude that the specificity of a 

 protein antigen is determined by the aromatic radicals. 



Landsteiner^ found that by esterifying proteins with acid alcohols, acetylating 

 with acid anhydride or acid chlorides, or by methylating with diazo methane, such 

 marked changes in specificity were produced that not only, for example, did an anti- 

 serum react with acetylated sera from widely different animal species, but also with 

 acetylated proteins from plants as well. These changes in specificity were as great 

 as those reported by Obermayer and Pick, but the chemical changes in the altered 

 proteins were not alike. Those reported by Landsteiner took place in the salt-forming 

 group, and were not made by the substitution of H-atoms in the aromatic nucleus. 



Still another type of change was produced when Landsteiner and LampP treated 

 rabbit serum with formaldehyde, presumably producing a change in the lysine radical 

 of the proteins. In this case the rabbit serum was so altered that it produced anti- 

 bodies in rabbits that reacted with the formaldehyde-treated rabbit serum, but not 

 with other formaldehyde-treated sera; rabbit serum had become antigenic for rabbits, 

 but species specificity was retained. 



Perhaps the most interesting of Landsteiner's experiments are those which he and 

 his co-workers have performed with azoproteins." They made a series of thirty-three 

 azoproteins by treating horse serum with diazotized amino compounds. By immuniz- 

 ing rabbits with these, they obtained a number of sera which precipitated all other 

 azoproteins which contained the same azo-compound, no matter whether the serum 

 with which it was combined was horse, chicken, or beef. Some sera were entirely 

 specific, reacting only with antigens containing the homologous compound; others 

 reacted with those made with compounds containing aromatic side-chains chemically 



' Obermayer, F., and Pick, E. P.: Wien. klin. Wchnschr., 19, 327. 1906. 



2 Landsteiner, K.: Biockeni. Ztschr., 58, 362. 1913; Landsteiner, K., and Jablons, B.: Ztschr. 

 f. Immunitatsforsch. u. exper. Therap., 21, 193. 1914. 



■5 Landsteiner, K., and Lampl, H.: ibid., 26, 133. 1917. 

 ''Landsteiner, K., and Lampl, H.: Biochem. Ztschr., 86, 343. 1918. 



