HEMAGGLUTINATION 47 



that this chemical breakdown is identical with inhibitor destruction has 

 not yet been published. 



On a biological level somewhat more is known about virus-receptor 

 systems of which the receptor gradient sequence is a good example 

 (Burnet, McCrea, and Stone, 1946). Red cells are exposed to a bacterial 

 filtrate for different lengths of time so that one has a series of prepara- 

 tions with varying proportions of intact receptors. These cells are tested 

 for their capacity to adsorb a series of virus strains of the MNI group. 

 It is found that the capacity of cells to adsorb some strains is rapidly 

 destroyed by the filtrate while other strains still adsorb well on cells 

 that have had a prolonged exposure and have presumably lost most of 

 their receptors. The arrangement of strains in the order in which their 

 receptors disappear constitutes the gradient series and a very large 

 number of strains can be so arranged, each a little different from the 

 other. The same phenomenon has been demonstrated with virus de- 

 struction of receptors. From this and other experiments it appears 

 probable that there are differences among cell receptors which are 

 manifest in varied susceptibility to destruction and varied ability to 

 combine with various strains. 



Burnet and his collaborators in addition to finding differences in 

 receptors have found differences in virus enzyme specificity which 

 correlate perfectly with the virus gradient. If a number of strains are 

 arranged in the order of their receptor gradient (1, 2, 3, 4, etc.), i.e. 

 the order of increasing resistance of their cellular receptors to enzy- 

 matic destruction, then the following also occurs: when viruses of the 

 gradient series are used for receptor destruction, strain 1 removes the 

 receptors of itself alone, strain 2 removes receptors for 1 and 2, strain 

 3 for 1, 2 and 3, etc. This result implies a higher degree of specificity 

 on the part of the virus enzyme. Such specificity was not present in 

 other experiments (Hirst, 1950^), where it was found that each strain 

 was capable of destroying the entire receptor complex provided the 

 virus was present in sufficient concentration and allowed to act for a 

 sufficient length of time. These two findings have not been reconciled. 

 In the latter experiments the viruses which destroyed receptors with 

 greatest speed also destroyed the receptor complex most completely, i.e. 

 they were highest in the receptor gradient. 



To explain the occurrence of a receptor gradient, Burnet postulated 

 a single class of receptors buried at different depths in the cell surface 

 and hence wdth varied ability to combine with virus and susceptibility 

 to virus destruction. As will be seen below, this hypothesis will scarcely 

 explain the behavior of inhibitors to virus action, and it seems at least 

 equally vahd to presume that the receptor site of the cell is a complex 



