Nature and Formation of Antibodies 



Felix Haurowitz 



Indiana University, Bloomington, Ind. 



THE HIGH SPECIFICITY of Serological reactions, that is, of reactions between 

 antigens and antibodies, was recognized at the end of the last century 

 and wide use was made of these reactions for the diagnosis of certain 

 diseases. However, there was no satisfactory scientific explanation for the bases 

 of this specificity. Paul Ehrlich, the famous German immunologist, assumed 

 complementariness in shape between antigen and antibody (Ehrlich, 1906), 

 although it was not clear at that time whether complementariness of cellular 

 shape or complementariness of subcellular particles or smaller units was meant. 

 One has to keep in mind that "antigen" at that time meant, in general, a bac- 

 terium or a red blood cell and that only later was it found that protein mole- 

 cules also can act as antigens. Nothing was known of the nature of antibodies. 

 ]\Iany immunologists attributed antibody function to an unknown physical- 

 chemical state of the immune serum rather than to definite antibody molecules. 

 Our present views on immunochemical reactions are based mainly on the 

 fundamental experiments of Landsteiner (1946), who discovered that serologi- 

 cal specificity is chemical specificity. Landsteiner introduced into serology the 

 coupling of proteins with diazotized aromatic amines and amino acids. He 

 proved that injection of proteins substituted by o-, m-, and ^-azophenylsul- 

 fonate groups gave rise to the formation of three different types of antibodies 

 and that antibodies differentiated not only between o-, m- and p-, but also 

 between cis- and trans- or d- and /-compounds. It became clear by these results 

 that serological specificity is not directed against the antigen molecule as an 

 entity but against a definite chemical group of the antigen molecule. 



A deeper insight into the problem of specificity was obtained by quantitative 

 analyses of the precipitate. The first analyses of this type were done by Hsien 

 Wu (1927). Shortly thereafter Heidelberger (1929) in this country and myself 

 with Breinl (1932) in Prague analyzed various antigen-antibody systems. 

 It became clear from these analyses that antigen and antibody combine accord- 

 ing to definite ratios and that antibodies are proteins. It had been known for 

 many years that the antibody function was linked to the globulins of the 

 immune serum. The general belief was, however, that these globulins were 

 contaminants of the true antibodies just as enzymes at that time were con- 

 sidered as unknown substances contaminated by proteins. In 1930, Breinl and 

 I came to the conclusion that antibodies were not "contaminated" by globulins 



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