THE NATURE OF THE ANTIGEN-ANTIBODY UNION 263 



a preparation that stimulates the production of antibodies to the azo compound 

 (Haurowitz 1937). 



The important observation of Bawden and Kleczkowski (1941, 1942a) that, when 

 antigens like bushy stunt virus or human serum globulin are heated in the presence 

 of a serum albumin, complexes are formed which, though non-precipitating, are 

 still antigens, demands a similar modification of the conception of antigenicity. 

 The antiserum to the albumin-globulin complex precipitated with globulin alone ; 

 the precipitation was inhibited by the complex, which in this respect behaved 

 like a hapten. There is no good reason to suppose that antigenic, but non-reacting 

 substances do not occur in nature. The examples from experimental serology 

 suggest that they may be discovered in the first case by reaction between the 

 " antiserum " and a heterologous antigen that happens to possess a large number 

 of the determinant groups characterizing the " antigen," and in the second case, 

 by reactions between " antiserum " and degradation products of the apparently 

 non-antigenic substance, though it would be hard to predict the kind of degrada- 

 tion processes likely to yield positive results. Bawden and Pirie (1944) have 

 provided a natural example of the first kind. Extracts of the leaves of tomatoes 

 infected with the bushy stunt virus contain a substance which, on injection into 

 rabbits, yields an antiserum that does not precipitate with the substance, but 

 precipitates with bushy stunt virus obtained from sap. In this case, the non- 

 precipitating antigenic complex consisted of virus and a chromoprotein ; on 

 separation, the former precipitated with the antibody, and the latter had an inhibit- 

 ing effect on this precipitation. 



The Nature o£ the Antigen-antibody Union. 



The large body of evidence makes it quite clear that the antibody receptor 

 is adapted with a high degree of precision to the surface of native antigens, and 

 that the adaptation is changed by imposing additional determinants on the anti- 

 genic surface. The nature of the adaptation is not clear. The surface of a large 

 molecule, which may as a whole be electrically neutral, is characterized by positively 

 or negatively charged atomic groupings, which create localized electric fields in 

 the immediate neighbourhood of the molecule, operative over a very short distance. 



When two molecules approach each other closely, these fields, if of opposite 

 sign, will cause an attraction. In large molecules — and it will be remembered 

 that it is with reactions between large molecules that we are mainly concerned — 

 the electric fields set up may be very numerous, and they will have a quite definite 

 spatial arrangement. Taken in conjunction with the shortness of the distance over 

 which these intermolecular forces are operative, this complexity and constancy of 

 pattern provide just the conditions required for specificity. Two molecules possess- 

 ing at their surface electric fields so arranged that, when they come into close contact, 

 there will be multiple points of attraction between them, will tend to adhere to one 

 another. Two molecules possessing the same number of electric fields, but 

 with these so arranged that close contact cannot be made at many points simultane- 

 ously, will show no tendency to adhere. The better the fit, in this specialized sense, 

 the greater will be the total force of attraction. 



One of the best available examples of the action of these intermolecular forces is 

 the selective formation of mixed crystals. The molecules involved must conform to 

 the required pattern in regard to their dimensions and the relative position of their 

 active groupings, or atoms. As a result most crystals consist of one kind of molecule 

 alone ; but molecules of different kinds may be built into a single crystal, provided 



