ENERGY OF ANTIBODY-ANTIGEN REACTIONS 143 



contributed by the term T ^S° and is thus due to the positive entropy 

 change (equation (25). 



In spite of the relative weakness of the antibody-antigen or anti- 

 body-hapten bond, antibodies display very sharp specificity, as we 

 have already seen. For instance, when Karush compared the reac- 

 tions of anti-"lac" antibody with lactose with the reaction of the 

 same antibody with cellobiose, he found a value for Ai^" of — 5.52 

 kcal. per mole for lactose and only — 1.96 kcal. per mole for celloboise, 

 although the only difference between the two sugars is the arrange- 

 ment of the hydrogen and hydroxyl groups on carbon number 4 

 of the terminal hexose unit (Fig. 10-4). This again accords with 

 the notion that the hapten fits quite precisely into a portion of the 

 antibody. 



The importance of close fit of antibody to hapten is also shown 

 by the work of Nisonoff and Pressman (1957) who found that 

 substitution of an iodine atom ortho to the carboxy group of the 

 benzoate ion decreased the antibody-hapten combining energy by 

 2.4 kcal. per mole. Substitution of an iodine in the meta position 

 decreased the binding energy by about 0.7 kcal. per mole. 



It has been known for some time that the antibody molecules in 

 any given antiserum are heterogenous (references in Boyd 1956). 

 This heterogeneity manifests itself, among other ways, by differences 

 in their specific affinity (Karush, 1958; Epstein, Doty, and Boyd, 

 1956; Nisonoff and Pressman, 1958). This means that the AF° 



CHjOH H 



Lactose 



