The cytotoxic moiety(ies) in highly purified streptococcal M protein has been shown to be distinct from the type-specific M determinant. This nontype-specific M-associated determinant(s) (NTSM) causes humoral and cellular immunotoxic responses in man. NTSM is common to M protein prepared from all streptococcal serotypes studied so far. In this study, immunoabsorbents prepared by entrapping purified M proteins in polyacrylamide gel were employed to identify, separate, and purify antibodies directed against NTSM as well as against the type-specific M (TSM) determinants. We found that anti-NTSM present in human blood mediated cytotoxic platelet and leukocyte reactions in the presence of "M proteins" prepared from groups A, C, and G streptococci. Human sera that produced cytotoxic reactions and fixed complement in the presence of highly purified M protein but that contained no antibody to the homologous TSM determinant were used as a source of anti-NTSM. Anti-NTSM was absorbed with and eluted from M protein-polyacrylamide particles and identified as IgG. Antibodies to NTSM were present in most normal human sera and some primate sera (rhesus monkey and baboons) but not in the sera of other common laboratory animals. Further absorption studies showed NTSM to be a component not only of extractable M protein but also of protoplast membranes and of cell walls of avirulent streptococci that lacked extractable TSM antigen. Preparation of antisera that can distinguish between the type-specific protective moiety and the closely associated immunotoxic components in purified M protein vaccines may help answer whether or not M-associated moieties play a role in pathogenesis of poststreptococcal diseases.

Absorption↗

PubMed1972

The common antigen(s) of streptococcal M protein vaccines causing hyperimmune reactions in man.

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Acrylamides↗

PubMed1971

Toxic effects of streptococcal M protein on platelets and polymorphonuclear leukocytes in human blood.

Purified M protein isolated from Group A streptococci produced cytotoxic reactions in normal human blood in vitro. In the presence of M antigen, platelets aggregated, fused, and lysed. Polymorphonuclear leukocytes (PMN) surrounded the platelet aggregates, then became highly vacuolated and lysed. In addition, PMN progressively lost their capacity to phagocytose unrelated bacteria and to migrate in glass capillary pipettes. Platelet-PMN reactions were directly proportional to the type-specific precipitin reactivity of each M preparation and could be removed with homologous M antibody, only. Moreover, the reactivity of M protein was abolished by enzymatic digestion with trypsin, but not with lysozyme, strongly suggesting that cell-wall mucopeptide was not involved. Preliminary studies showed that platelet-PMN reactions require heat-stable and heat-labile serum factors, presumably antibody and complement. It is suggested that cytotoxic determinants are uncovered by the extraction and purification process and are intimately associated with the type-specific M determinant, possibly in a molecular complex.

Agglutination Tests↗

PubMed1971