Molecular Complemeiitariness in Antigen- 

 Antibody Systems 



David Pressman 



Roswell Park Memorial Institute, Buffalo, N. Y. 



IN MANY EXAMPLES of biological specilicily there appears to be a close com- 

 plementariness of fit of the active site of the receptor molecule about its 

 substrate, so that enough of the various weak, short-range forces, such as 

 the van der Waals forces, charge interaction, hydrogen bond, dipole interaction 

 and so forth, can be effective in holding molecules together (Pauling, Campbell 

 and Pressman, 1943; Pressman, 1953). 



Specificity arises from the fact that only certain configurations can fit the 

 site; other configurations are blocked sterically so that they cannot fit. 



The study of hapten-antibody interactions permits the determination in a 

 particular specific system of just how close the fit is, and what forces are acting. 

 This is so because antibodies can be formed against simple chemical substances 

 of known configuration and the contour of the antibody's specific site can then 

 be determined more or less precisely, or felt out, by the interaction of that site 

 with substances of known configuration. 



The studies of hapten-antibody interactions discussed here stem from the 

 voluminous pioneer studies of Landsteiner (1945) on chemically altered pro- 

 teins and the antibodies dervied therefrom. 



The extent of combination of a hapten with an antibody which is directed 

 against it can be determined either by partition of the hapten between an anti- 

 body solution and a control solution, as was first carried out by Dr. Haurowitz, 

 (1933) our next speaker, and by Marrack and Smith (1932), or by the ability 

 of the hapten to combine with the antibody and inhibit the precipitation of 

 that antibody by the homologous antigen, as in the extensive studies by Land- 

 steiner. 



The studies which I shall be reporting here were carried out initially under 

 Dr. Linus Pauling's direction at the California Institute of Technology and 

 subsequently at the Sloan-Kettering Listitute and now at the Roswell Park 

 ^Memorial Institute. Some of the work reported here, as yet unpublished, was 

 done by Dr. Nisonoff, who is now at Roswell Park with me. 



An antibody acts as though it were formed against the antigen as a template. 

 It is important to realize that the orientation of the hapten with respect to 

 the antigen surface during antibody formation is a prime factor. Fig. 1 shows 

 three such orientations for a hapten, /?(/>'-azobenzeneazo) benzoate, attached 



