Heterogeneous Antigens

HETEROGENEOUS ANTIGENS and heterogeneous antibodies, a concept introduced into science by Friedberger to distinguish alien, in a species sense, biochemical complexes that exist in a whole series of animals alongside species-specific antigens and antibodies (homologous antigens and antibodies). The first heterogeneous antigen was discovered by the Swedish scientist Forssman in 1911 in the organs of the guinea pig. It turned out that the organs of this animal, belonging to the order of rodents, contain an antigen of another species, belonging to a representative of a very distant order, the ungulates—the sheep. Even more striking facts began to be revealed later. It was established that the same sheep antigen is found not only in different species within the order of mammals, but also in animals of other classes—birds, reptiles, and fish (Tsunoda, Kaljaev). It is probable that the same heterogeneous antigen is found in plants, and there is data on its presence in bacteria (Bacterium dysenteriae Shiga, Bacterium lepisepticum). Subsequently, primarily Krichevskii and his colleagues showed that heterogeneous antigens can be those of many other species of animals, in addition to the sheep antigen, now called, by the proposal of Tanigusi, the Forssman antigen. So far, antigens of the chicken, turtle, cat, pig, human, crucian carp, and carp have become known. However, it is possible that both the heterogeneous antigen of the sheep and all the heterogeneous antigens of other animals just listed are actually a single biochemical complex. This assumption is all the more probable because the separate existence of one heterogeneous antigen has never been recorded, while all heterogeneous substrates are always present together. Since the heterogeneous antigen of the sheep was detected only in organs and was not found in the erythrocytes of animals, Doerr and Pick formulated the position that the heterogeneous antigen, in contrast to the homologous one, being present only in organs, is absent in the erythrocytes of the corresponding species. However, soon this law was refuted by Krichevskii, and subsequently Schiff, Hyde, and Vitebsky agreed with him. Antibodies that are formed upon immunization of animals with cells containing heterogeneous antigens are also called heterogeneous, in accordance with the latter. Forssman himself obtained only heterogeneous hemolysins and hemagglutinins. But then Krichevskii and Amako (Atsuo) realized heterogeneous anaphylaxis; subsequently, heterogeneous precipitins (flocculins) of Sordelli and Pico, as well as Sachs and Gut, were also discovered; Tanigusi proved the presence of heterogeneous antibodies binding complement, and Krichevskii and Lebedeva—heterogeneous cytotropins. The facts set forth above clearly showed that the doctrine of species specificity of immune bodies must be considered refuted. Attempts by supporters of the incontestability of this doctrine to prove a different mechanism of formation of heterogeneous antibodies compared to homologous ones, based on the toxicity of organs which, it was claimed, alone could serve as antigens, were soon discredited by the aforementioned researches of Krichevskii, which showed that these antibodies are brought to life, just like the homologous ones, also by red blood cells devoid of toxicity. At the present time, this absence of species specificity in antibodies as a theoretical principle can be considered already accepted by all. Only the school of Sachs is now trying to replace the position on species specificity with the doctrine of receptor specificity. The physicochemical properties of heterogeneous antigens are very peculiar. The latter possess great heat stability, withstanding many hours of boiling without harm (Doerr, Pick), and, what is especially important, are soluble in alcohol. The discovery of this property has more significance in the history of the science of immunity than the very discovery by Forssman of the first heterogeneous substrate, since it paved the way for the study of the nature of antigens. The fact is that Tanigusi, and independently of him, Sordelli and Fischer discovered that lipid solutions of heterogeneous antigens possess the ability to bind corresponding antibodies, without being able to cause their formation upon immunization of animals. These authors were the first to show that the ability of antigens to bind antibodies and the ability to cause their formation, considered until then inseparable from one another in the antigen molecule, are in reality different and localized in different complexes. Thus, incomplete antigens, which are lipoids and later named haptens by Landsteiner, became known. Since in science previously the view was established on antigens as exclusively protein substances, the discovery of lipid antigens, although incomplete, caused a great shift in our views on the nature of antigens and an upsurge of work in this area. The latter has already led to the discovery of the fact of the existence of other incomplete antigens—polysaccharides—and a significant deepening and expansion of our knowledge on the essence of antigens.