Sequence of protective epitopes of streptococcal M proteins shared with cardiac sarcolemmal membranes.

Synthetic peptide fragments spanning the entire amino acid sequence of pep M5 were used to detect epitopes cross-reactive with heart tissue components other than myosin. Heart-cross-reactive pep M5 antibodies were affinity purified by absorption to and elution from purified sarcolemmal membranes. Only one of the synthetic peptides, SM5(164-197)C, inhibited reactivity of the affinity-purified antibodies with pep M5 by ELISA. SM5(164-197)C linked to KLH evoked both opsonic and heart-cross-reactive antibodies in rabbits. In addition to type 5, the immune sera opsonized M types 6, 18, 19, and 49 streptococci. The antisera reacted strongly with isolated cardiac sarcolemmal membranes by immunofluorescence. In Western blots of cardiac tissue, the anti-SM5(164-197)C reacted with a 40 kDa protein but not with myosin. The reaction was inhibited by pep M5 and SM5(164-197)C but not by any of the other peptides spanning pep M5. The cross-reactive anti-SM5(164-197)C affinity purified on sarcolemmal membranes opsonized types 5, 6, and 19 but not type 24 streptococci. These results indicate that SM5(164-197)C contains heart-cross-reactive, opsonic epitopes that are shared among heterologous serotypes of group A streptococci.