l8 BRENT, MEDAWAR AND RUSZKIEWICZ 



In two experiments, antigenicity was abolished by tryptic 

 digestion for 15 to 30 min. at room temperature. It will be seen 

 from Table V that the injection of heated C3H "antigen" into 

 C3H mice had no effect on the survival time of homografts, a 

 result which seems to rule out a non-specific activation of the 

 host's response.* 



The upshot of the experiments described in the last two sections 

 is that antigenic matter lacking in detectable serological activity 

 may yet sensitize against homografts in vivo. It is not yet possible 

 to distinguish between the following explanations of this fact: (i) 

 the residual sensitizing activity belongs to an antigen of the H-2 

 complex, but the combining sites necessary for the absorption or 

 inhibition of antibody in vitro are rendered inaccessible by 

 physical changes accompanying denaturation ; or (2) there is a 

 genuine difference between "X" forms and "H" forms of iso- 

 antigens (in the terminology of Mcdawar (1959)), the former 

 being the more stable. This second interpretation now carries little 

 conviction. A third possibility, (3), is that the many antigens by 

 which strain A differs from strain C3H — antigens governed by 

 loci other than H-2 — are a chemically heterogeneous assemblage 

 (cf. Berrian and Jacobs, 1959), and that some are thermostable or 

 resistant to lipid solvents. This seems at present to be the most 

 plausible explanation ; the chief obstacle in the way of accepting 

 it is that we should not expect these weaker antigens to be revealed 

 by a test in which the skin graft used to measure the degree of 

 sensitivity is transplanted as soon as three days after the sensitizing 

 injection. 



Summary 



It is shown that the physical form and route of ingress of 

 sensitizing cellular extracts affect their immunological perfor- 



* The injection of "antigen" of syngeneic (isologous) origin is the most 

 convincing test of specificity of action when a complex of sensitizing antigens of 

 different genetic determination is distributed in an unknown manner among the 

 various inbred strains of mice. 



