EPITOPES OF STREPTOCOCCAL-M PROTEINS THAT EVOKE ANTIBODIES THAT CROSS-REACT WITH HUMAN BRAIN

There is evidence suggesting that Sydenham's chorea, which is a major manifestation of acute rheumatic fever, may be mediated by streptococc al antibodies that cross-react with the brain. Our studies were undert aken to determine whether streptococcal M protein, the major virulence factor of group A streptococci, evokes antibodies that cross-react wi th human brain. Rabbits were immunized with pepsin-extracted M protein from rheumatogenic type 6 streptococci. Immune sera were screened for the presence of antibodies that cross-reacted with human brain by ind irect immunofluorescence tests and immunoblot analyses. Type 6 M prote in evoked antibodies that cross-reacted with several brain proteins an d antibody binding to these proteins was completely inhibited by type 6 M protein and partially inhibited by types 5 and 19 M proteins, sugg esting that these heterologous M proteins contain conserved brain-cros s-reactive epitopes. Using synthetic peptides from several serotypes o f M proteins, the conserved brain-cross-reactive epitopes were localiz ed to a decapeptide contained within the covalent structure of the B r epeat region of type 6 M protein. These peptides also inhibited brain- cross-reactive antibodies in the serum of a patient with active Sydenh am's chorea. Our data indicate that streptococcal M proteins contain b rain-cross-reactive epitopes that could potentially be involved in the pathogenesis of Sydenham's chorea.