Myosin: A Link Between Streptococci and Heart

Abstract

Murine monoclonal antibodies to Streptococcus pyogenes reacted with skeletal muscle myosin. High molecular weight proteins in extracts of human heart tissue that reacted with an antibody to S. pyogenes also reacted with a monoclonal antibody to ventricular myosin. Adsorption of the antibody to streptococci with S. pyogenes simultaneously removed reactivity of the antibody for either S. pyogenes or myosin. These results indicate that myosin shares immunodeterminants with a component of S. pyogenes.

Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection

“…The kinetics and specificity of many of the antibody responses have been characterized in human infection (Mote and Jones, 1941;Rothbard et al, 1948;Stollerman et al, 1956;Denny et al, 1957). In the susceptible host, autoreactivity of this response (in particular crossreacting anti-M protein antibody) may contribute to the pathogenesis of acute rheumatic fever (Kaplan and Svec, 1964;Zabriskie et al, 1970;Krisher and Cunningham, 1985;Cunningham et al, 1989).…”

Cardiac Myosin and the TH1/TH2 Paradigm in Autoimmune Myocarditis

“…18,20 -27 In 1985, myosin was identified as an autoantigen involved in cross-reactivity between the group A streptococcus and heart. 28 Since this time, evidence has supported the molecular mimicry hypothesis that streptococcal M protein and the group A carbohydrate both induce anti-myosin responses that attack the heart. 22,29 -33 In fact, immunological mimicry was demonstrated between streptococcal M protein and myocarditic coxsackieviruses and was linked to cytotoxic antibody against heart cells as well as T lymphocyte responses.…”

Tubulin Is a Neuronal Target of Autoantibodies in Sydenham’s Chorea

“…It has been well-documented that group A streptococci promote the generation of cross-reactive or polyreactive Abs through molecular mimicry between streptococcal and host Ags (5,7). Cross-reactive Abs, particularly against the group A carbohydrate Ag, may play a role in the clinical manifestations of ARF (3,4).…”

“…Importantly, previous studies using murine and human mAbs from patients with ARF identified the GlcNAc epitope as well as group A streptococcal M protein as cross-reactive streptococcal Ags capable of cross-reactivity with host ␣-helical proteins including myosin, tropomyosin, keratin, vimentin, and laminin. The crossreactivity demonstrated that Abs were capable of binding Ags of different molecular compositions (1,3,10,(15)(16)(17). Although molecular mimicry between GlcNAc and cytoskeletal proteins has been characterized in heart disease, similar cross-reactivity with ␣-helical proteins has not been investigated in rheumatic streptococcal neurological disorders.…”