The J substance of cattle, and the R and r (formerly called O) substances of sheep, are heritable constituents primarily of the serum of individuals within each species. The presence of these substances on the erythrocytes is presumably dependent on their presence in the serum.

Cattle sera contain antibodies which are reactive with all groups of human and sheep cells. The sera of cattle with the J substance not infrequently contain antibodies with different specificities towards human cells, and within this class occasionally can be found a serum with antibodies strongly reactive with human O cells. In contrast, anti-J sera of cattle are reactive not only with J cells of cattle, but also are strongly reactive with A and AB of humans, even more strongly reactive with sheep R cells, and considerably less strongly reactive with r cells of sheep and with human cells carrying O or B.

Four different specificities were demonstrable in anti-J sera of cattle. The absorption of antibodies in anti-J serum by J cells of cattle, R of sheep and A of humans is clearly paralleled by the ability of cattle serum with J, sheep serum with R and saliva from human secretors of group A to inhibit the lytic reaction of anti-J with both J (cattle) and R (sheep) cells. These various results indicate that the major specificity of the antibodies in anti-J serum is directed against antigenic specificities common to cattle J, sheep R and human A. A second weaker specificity of anti-J serum appears to be directed against sheep R and human A cells but not cattle J, while additional specificities are generally present in the sera of cattle and are presumably species specific antibodies for the cells of sheep and humans, respectively.

The anti-R of sheep serum is reactive with sheep R and human A and O cells, but not with cattle J cells. However, cattle serum containing J will inhibit the reaction of anti-R with R cells though only in low dilutions. Anti-R serum is inhibited also by high dilutions of sheep serum with R and human saliva from secretors of A.

The antibodies in exceptional cattle sera which are specifically reactive with sheep r are also reactive with human A, B and O cells, and are absorbed by A and B, but not by O cells. These antibodies are inhibited by the serum of sheep with r on their cells, and by the saliva of (human) secretors.

Human anti-A serum is moderately reactive with cattle and sheep cells, but presumably by virtue of respective species specific antibodies rather than of antibodies cross-reactive with the J and R substances.

Despite the different specificities among, and probably within, anti-J sera of cattle, anti-R of sheep, and anti-A of humans, the evidence indicates strongly an antigenic relationship of the J substance of cattle, R of sheep and A of man. This is noteworthy because the J and R substances are primarily soluble substances of the serum of cattle and sheep, respectively, whereas the A substance of the red cells of man, as contrasted to the secretory product, is a constituent of the blood cells. The findings further support the view that some agglutinogens, perhaps all, behave serologically as if they have a complex mosaic structure, so that each agglutinogen is characterized by multiple antigenic factors.

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