528 F. M. BURNET 



up into a visible aggregate or by its newly developed surface qualities adsorbs 

 complement. Most neutralization tests with viruses do not necessarily involve 

 aggregation but, when concentrations and conditions are appropriate, classic 

 aggregation reactions can probably be demonstrated with any virus. There 

 are a number of instances where virus-neutralizing antibody can be shown to 

 act also as a precipitin or complement-fixing antibody and, with qualifications 

 based on the possible presence of a variety of antigens on the surface of 

 some viruses, most workers beUeve that the two types of antibody are 

 identical. 



The classic theory of the precipitm reaction, due to Heidelberger and 

 Kendall (1935) and uifluenced much by Marrack's (1934) ideas on lattice for- 

 mation, may be used as a basis for the discussion of virus-antibody reactions 

 as for any type of antigen-antibody reaction. 



In this view, reaction takes place between determinant groups, of which 

 there are usually multiple examples on each antigenic molecule or particle, 

 and complementarily patterned groupings on antibody molecules. There is 

 evidence to suggest that there are two such specifically patterned areas on 

 standard antibody globuhn molecules (Marrack et al., 1950; Singer and 

 Campbell, 1951). In a recent review of the nature of antigen-antibody aggre- 

 gates, Marrack (1955) considers that the approach of Goldberg (1952) provides 

 the most physically satisfactory picture of the process. According to this view, 

 all reactions are reversible and union will take place according to the prin- 

 ciple of maximal entropy. The primary aggregates w4th a soluble protein 

 antigen will be mostly in the form of branched chains with little formation 

 of cychc (lattice) structures. Further aggregation is dependent on ionic 

 content and varies according to the species furnishing the antiserum and 

 other factors. With excess of antigen, precipitation fails to occur and with 

 toxin-horse antitoxin systems, precipitation also fails in the presence of 

 excess of serum. 



Union between two complementary configurations on antigen and antibody 

 ]/ seems unlikely to be expressible in simple mass action terms. For union to 

 occur an appropriate steric orientation will be required and it may be that a 

 provisional ionic miion of some sort is needed to allow the definitive specific 

 union to take place. Nothing is really known about the "goodness of fit" 

 between a given antibody and antigen, but there is much experimental and 

 theoretical reason to believe that wide variations in this quality must exist. 

 Where antigenic molecules are embedded in the complex environment of a 

 particle surface, as in a virus, there must be a still greater range of oppor- 

 tunity for various degrees of partial union. In the classic antigen-antibody 

 reaction, the globulin of the antibody is denatured and rendered insoluble. 

 The conditions under which union of an antibody globulin molecule to an 

 antigenic molecule or surface results m its denaturation have not been 



