Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever.
The antigenic relatedness of surface-exposed portions of M protein molecules derived from group A streptococcal isolates representing more than 50 distinct serotypes was examined. The data indicate that the majority of serotypes fall into two major classes. Class I M protein molecules share a surface-exposed, antigenic domain comprising the C repeat region defined for M6 protein. The C repeat region of M6 protein is located adjacent to the COOH-terminal side of the pepsin-susceptible site. In contrast, Class I M proteins display considerably less antigenic relatedness to the B repeat region of M6 protein, which lies immediately NH2-terminal to the pepsin site. Surface-exposed portions of Class II M proteins lack antigenic epitopes that define the Class I molecules. Studies in the 1970s demonstrated that M protein serotypes can be divided into two groups based on both immunoreactivity directed to an unknown surface antigen (termed M-associated protein) and production of serum opacity factor. These two groups closely parallel our current definition of Class I and Class II serotypes. Both classes retain the antiphagocytic property characteristic of M protein, and Class II M proteins share some immunodeterminants with Class I M proteins, although the shared determinants do not appear to be exposed on the streptococcal surface. Nearly all streptococcal serotypes associated with outbreaks of acute rheumatic fever express M protein of a Class I serotype. Thus, the surface-exposed, conserved C repeat domain of Class I serotypes may be a virulence determinant for rheumatic fever.
Bessen
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D
Rockefeller University, New York, New York 10021.
Jones
K F
KF
Fischetti
V A
VA
D000942:Antigens, Bacterial / Q000032:analysis* / Q000145:classification; D000954:Antigens, Surface / Q000032:analysis / Q000145:classification; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000145:classification* / Q000276:immunology / Q000648:ultrastructure; D015153:Blotting, Western; D002352:Carrier Proteins; D009842:Oligopeptides / Q000276:immunology; D010447:Peptide Hydrolases / Q000096:biosynthesis; D012213:Rheumatic Fever / Q000382:microbiology*; D012703:Serotyping; D013297:Streptococcus pyogenes / Q000145:classification / Q000472:pathogenicity*
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D009842:Oligopeptides; C021908:opacity factor; C014689:streptococcal M protein; D010447:Peptide Hydrolases