530 F. M. BURNET 



immune sera with heterologous strains he could obtain monovalent reagents, 

 which allowed the recognition of a series of new antigens emergmg irregidarly 

 over the years. In some sense this is undoubtedly an artifact. The important 

 question is not whether there is change in antigenic structure, but whether 

 there is any intrinsic regularity in the changes. If the atove hypothesis is 

 correct, it should be possible by appropriate heterologous absorptions to 

 make the number of steps as many or as few as one desires. From the lack of 

 concordance among those who have used the method, it seems very probable 

 that this is in fact the case. 



Another point that it is desirable to keep in mind is the varying antigenic 

 potency of antigens and, by impHcation, of determinant groups. Some 

 proteins, hke gelatin, are virtually nonantigenic; some bacterial \Truses, like 

 C16 and T2, produce high titer antisera with the greatest ease; others, like 

 S8, produce minimal titers only (Burnet, 1933b). Landsteiner (1946) found 

 some of his azoproteins much more effective in producing specific antibody 

 than others. Although it is hard to envisage how an experimental test of the 

 point might be made, it seems certain that antibody molecules can differ in 

 their effectiveness of union with the corresponding antigenic determinant. 

 The simplest explanation of incomplete (or monovalent) antibody is that such 

 molecules can make only a weak, highly reversible union unless they are 

 trapped, as it were, in the lattice formed by antibody molecules of full 

 avidity. The sum of these contentions is that the complexity of the situation 

 when antiserum reacts with antigenic material is far too great to make it 

 justifiable to do more than look cautiously for broad analogies with simple 

 chemical systems to which the elementary law^s of physical chemistry can be 

 apphed. In any system of significance for virology, we are concerned with 

 antigenic molecules embedded in a complex particulate system. The system 

 that is effectively concerned with antibody production, i.e., the virus particle 

 presumably in the process of disintegration in cells of the antibody-producing 

 system of the host, is also different from the vims particle with w^hich the 

 antiserum reacts in any experimental test. This may be responsible for certain 

 asymmetrical antigenic relations between virus strains. Stram A may 

 produce antibody which reacts more actively with strain B than with itself, 

 as in van der Veen and Mulder's (1950) P-Q phenomenon m mfluenza viruses. 



III. Aggregation Reactions in Virology 



Aggregation reactions with qualities intermediate between the specific 

 precipitation of a soluble antigen and immune agglutination of bacteria can 

 be observed whenever preparations of sufficiently high virus content and 

 active antisera are available for test. Except in the plant virus field they 

 have not been extensively used. Complement fixation has, however, become 



