26 INTRODUCTION TO IMMUNOCHEMICAL SPECIFICITY 



glucose and galactose, which, in view of the fact that a- and y8-glucose 

 are spontaneously interconvertible in solution, seems reasonable. 



Limitations of Specificity 



It is apparent from this and similar work, that though the power 

 of antibodies to distinguish small chemical differences in antigens is 

 very considerable, this discrimination has certain limits, limits which, 

 in the case of the alpha and beta anomers of glucose, we have almost 

 reached. The number of different antibodies is certainly large, but 

 we are moved to ask : Is there perhaps a limit to the number of 

 substances which can be distinguished serologically? 



We have by no means tested all possibilities, but I believe that the 

 answer to the above question is that there probably is a limit. In 

 the first place, cross-reactions are regularly found with closely re- 

 lated antigenic determinants (haptens), as we have just seen. In 

 the second place, antibodies to natural antigens are not directed 

 toward the molecules as a whole but toward relatively restricted por- 

 tions of the molecule (Chapter 3). These restricted portions of the 

 molecule consist of amino acid residues and combinations of amino 

 acid residues in the case of proteins and, in the case of carbohydrates, 

 of monosaccharide residues and combinations of monosaccharide resi- 

 dues. The number of amino acid residues occurring naturally is only 

 somewhat greater than twenty (Yeas, 1958). The number of mono- 

 saccharide residues occurring in any considerable amount in nature 

 is probably not much greater. The number of possible antigenic 

 specificities is therefore not infinite. It is accordingly not surprising 

 that, as more and more cross-reactions between antigens of unrelated 

 or remotely related origins are tried, more and more cross-reactions 

 are found to take place. 



Thus, cross-reaction occurs between human blood group A sub- 

 stance and pneumococcus type 14 capsular polysaccharide (Finland 

 and Curnen, 1940). Anti-pneumococcus type 14 sera strongly cross- 

 react with a galactan isolated from cow lung (Heidelberger and 

 Wolfram, 1954). Pneumococcus type 2 capsular polysaccharide and 

 the polysaccharide from encapsulated type B Friedlander bacillus 

 cross-react (Avery, Heidelberger, and Goebel, 1925). Highly active 

 substances with specificity similar to that of the human blood group 



