Immunological cross-reactivity between Streptococcus mutans and human heart tissue examined by cross-immunization experiments

Abstract

Hyperimmunization of rabbits with Streptococcus mutans or other related cariogenic streptococci sometimes induces serum antibodies that react with human heart muscle. To determine whether antigen I/II (AgI/II), a major surface protein antigen present in most human isolates of these organisms, was responsible for inducing cross-reactive antibodies, we tested it for antigenic similarity to heart components, exploiting the ability of immune systems to mount anamnestic responses to antigens previously encountered. Mice immunized with a strain of Streptococcus pyogenes type M6, known to be heart cross-reactive, or with intact S. mutans cells developed antibodies that could be detected on a human heart sarcolemmal preparation. However, mice immunized with AgI/II and boosted with sarcolemma were unable to develop significant antisarcolemmal antibodies attributable to prior sensitization by AgI/II. Similarly, AgI/II was unable to recall antisarcolemmal responses in mice previously immunized with sarcolemma. Nevertheless, strong immunoglobulin G antibody responses to AgI/II were detected at the single-cell level in spleens and as circulating antibodies in all mice immunized with AgI/II or AgI/II-bearing S. mutans. We conclude that the ability of S. mutans to induce heart-reactive antibodies is not due to antigenic similarity between AgI/II and components of human heart but may be caused by other cross-reactive antigens in the bacterial cells or by nonspecific stimulation of the immune system.