THE NATURE OF THE ANTIGEN-ANTIBODY UNION 265 



specificity must depend on the existence of an area on the surface of the antibody- 

 molecule that is in structure complementary to an area on the antigen molecule, 

 enabling large surfaces to approach close enough for the forces to operate over a high 

 proportion of the area of contact. Van der Waals' forces, for example, decrease as 

 the 7th power of the distance and are active only at distances of 0-1 to 0-3 m^/. 



The complementary nature of the two surfaces must include adaptation on the 

 part of the antibody to different determinants, their spatial relationships, and 

 the relative accessibiUty of the various groups. Cross-reactions between hetero- 

 logous antigens and antibodies, when there is good reason to believe they are due 

 to a monospecific antibody, and not to other types of antibody in the antiserum, 

 would result from the juxtaposition of less complementary areas, so that the 

 attractions are feebler, the dissociation of the antigen-antibody link greater, and, 

 as has been observed, the inhibition with haptens more effective, than in homo- 

 logous reactions (Landsteiner and van der Scheer 1936). 



Since it is likely that added determinants protrude from the surface of " syn- 

 thetic " antigens, Hooker and Boyd (1942) suggest that the corresponding surface 

 of the antibody is a depression. Indeed it may be that a spatial protrusion is 

 a necessary condition for determinant action. This speculation is supported by 

 the failure of all attempts to produce specific anti-antibodies, for if the antibody 

 receptors were depressions on the surface of the globulin molecule they would 

 on this basis have no determinant action. The anti-antibodies, as we have seen, 

 react equally well with normal globulins from the same animal, and, when they 

 react with the antibodies, do not interfere with the original antibody receptors. 



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