254 M. R. IRWIN 



of the two systems, or series, would then be produced by a series of multiple 

 alleles. The possibility of pseudo-alleles cannot be eliminated, but for the 

 present may be assumed not to be a complicating factor. 



If the assumption be granted that a single gene controls an antigenic com- 

 plex, as BGK, what explanation or explanations can be proposed for the dif- 

 ferent antigenic specificities of this and other complexes, and, in turn, what 

 can be inferred from such an explanation as to the action of the causative 

 gene? 



Antigens of Pneumococci 



By virtue of the ability to attach simple chemical compounds to proteins, 

 thereby preparing conjugated antigens with specifically reacting components 

 of known constitution, there has emerged from such studies the realization 

 that a so-called single antigenic substance may engender a multiplicity of 

 antibodies of varying specificities (see Landsteiner, 1945, for a critical review 

 and references). A pertinent example of this sort may be found in the anti- 

 genic relationship existing between type III and type VIII pneumococci. 

 Cross reactions between the respective antisera (produced in horses) and the 

 two types of pneumococci have been observed, implying to them some sort of 

 antigenic similarity. 



As is well known, the specificities of the pneumococcal types depend upon 

 the carbohydrates of the capsules (Heidelberger and Avery, 1923, 1924). 

 Thus, the carbohydrate of type III has been found to be a polyaldobionic 

 acid (Reeves and Goebel, 1941). The understanding of the structure of the 

 polysaccharide of type VIII is not as complete as for type III, but about 60 

 per cent of the molecule of the carbohydrate of type VIII appears to be 

 aldobionic acid. Cross reactivity may therefore be expected between the 

 soluble specific substances of types III (S III) and VIII (S VIII), by virtue 

 of the presence in each of multiples of the same aldobionic acid as a structural 

 unit. It is probable that the serologically reactive unit in each of these two 

 types is a larger portion of the polysaccharide molecule than a single chemical 

 structural unit. Type S VIII also contains approximately two glucose mole- 

 cules for every aldobionic acid residue, thereby presumably accounting for at 

 least a part of the specificity of type VIII in contrast to type III. Thus it may 

 be seen that serological cross reactions may be expected when the antigenic 

 substances under comparison are closely related chemically. Also to be ex- 

 pected is the ability to distinguish between such substances, as was actually 

 possible in the case of types III and VIII (Heidelberger, Kabat, and Meyer, 



1942). 



Genetic Significance 



The above example may be combined with other findings in the field of im- 

 munochemistry to allow the statement that antigenic substances of related 

 but not identical chemical constitution may — but sometimes do not — incite 

 the production of cross reacting antibodies. From the serological point of 



