The Biochemical Target of Flexner Dysentery Somatic Antigen

The effect of various harmful substances on proteins of living cells and the response of the proteins to stimulus from such compounds are of interest in many biological problems, such as growth, immunity, disease processes, etc. The little-known stimulus and response phenomena in this field could be investigated if there were available some specific system composed of a purified protein as the target on the one hand and of a known harmful agent on the other. Certain bacterial extracts and purified toxins have been shown to produce symptoms of disease upon injection of milligram or even microgram amounts in animals and man. In the case of some of these toxins it is possible that the chain of events leading to displacement of the body from the stable to the diseased state is initiated to some extent by direct, specific inhibition of some enzyme system. As part of the reaction to such an effect it seems possible, in view of the normal rapid process of regeneration which proteins undergo, that the regenerative processes in those enzyme systems injured by a toxin play a role in the production of immunity. The possible role of such enzymes in the development of the diseased state and of immunity could be investigated with an appropriate system composed of purified antigenic toxin and its biochemical target in the host. However, very little is known of specific effects of antigenic toxins in disease. As a first step in finding a measurable system, we have sought the physiological target of Flexner dysentery somatic antigen by measuring the radioactivity present in various organs of the rat after administration of a purified preparation of the antigen labeled with 1131. By seeking a target we wish to approach the problem simply and without assumptions as to the mechanism of infection and disease. We wish to describe as far as possible what this toxic antigenic material does in the host. "Target" refers to the system of receptors, whatever they may be. Critical analysis of present understanding"'9 ''' 16-19 regarding the loci of the interaction of this toxic antigen with cells permits no definite conclu-