34H IMMUNOGENETICS 



the users of this paper, and it will be toward that part of our subject that attention will 

 mainly be directed. 



A few of the general terms and concepts of immunology should be introduced at 

 the start: 



Antigens are molecules with two properties: first, they will induce an antibody 

 response when injected into an animal, and second, they will react specifically with the 

 antibodies they have induced. Often, the term antigen is not defined on a molecular 

 basis; for example, a red-cell suspension injected into an animal may be described as 

 the "antigen" injected. In general under such circumstances, one should recognize 

 that this gross "antigen" is composed of a number of discrete molecular antigens, each 

 involved in its own antigen-antibody reaction systems. Sometimes, a molecular 

 antigen is found to be unable to induce antibody formation although it is able to react 

 with antibodies evoked by a related material. For example, a fragment of a protein 

 may be able to react with the antibody induced by the intact protein, although the 

 fragment itself when injected may not give rise to a detectable antibody response. In 

 general, in order to be a complete antigen in the sense of both inducing and reacting 

 with antibodies, a molecule needs to be relatively large; most of them are in excess of 

 40,000 molecular weight, and many are in the millions. A small molecule, however, 

 such as a substituted benzene ring, may react specifically with antibodies; the reactive 

 sites on antibody molecules are themselves only small parts of the molecules. 672 Thus, 

 a complete, macromolecular antigen is conceived as being composed of numerous 

 individually small sites on sections of its surface, each site capable of reacting with 

 antibodies specific for it. These sites are spoken of as valence sites; complete antigens 

 are polyvalent and complete antibodies have two valence sites per antibody molecule. 

 The two valence sites on an antibody molecule seem to be identical with each other. 

 Very small reactive compounds may appear to act as antigens, as in idiosyncrasies for 

 particular drugs like aspirin, or dermal hypersensitivities to small compounds such as 

 picryl chloride. In such cases, it is generally assumed that the small molecule com- 

 plexes with larger ones in the recipient's system; it is the macromolecular complex that 

 acts as a complete antigen, the strange small added grouping being responsible for the 

 foreignness of the total molecule and directing the specificity of the antibody response 

 and reactions. 



Antibodies are modified serum globulins, secreted into the circulation by cells of the 

 antibody-forming series as a consequence of the injection of a foreign material and 

 specifically reactive with the material that caused their formation and release. The 

 basis for this remarkable adaptive response on the part of the injected animal is a 

 fascinating problem in somatic-cell genetics, currently under scrutiny and debate. 

 The easiest antibodies to discern are those that result in a visible reaction with the anti- 

 gen in ordinary media in test tubes, such as the agglutination of red cells in saline or 

 the precipitation of a soluble antigen from saline solution. Such reactions can be 

 formally conceived as involving two processes: first, the specific combination of antibody 

 molecules with sites on the antigen, and second, a derivative reaction in which a visible 



