Differentiation between two biologically distinct classes of group A streptococci by limited substitutions of amino acids within the shared region of M protein-like molecules.
Group A streptococci can be categorized into two classes (I and II) based on immunodeterminants contained within a surface-exposed, conserved region (C repeat domain) of the major virulence factor, M protein. Previous studies have shown that several biological properties correlate strongly with streptococcal class, and thus, there is a strong impetus to precisely define the antigenic epitopes unique to class I and II M proteins. Using synthetic peptides, the binding sites of two class I-specific mAbs were mapped to distinct epitopes within the C repeat region of type 6 M protein (class I). A class II M protein-like gene (type 2) was cloned and sequenced, and the predicted amino acid sequence was compared for homology to class I and II molecules, whose sequences were previously reported. For a given C repeat block 35 amino acid residues in length, 20 residue positions were conserved among all sequences analyzed. Of the 15 variable amino acid positions, only four were class specific, and three of the four positions were localized in the area to which the class I-specific mAbs bound. The predicted secondary structures of class I and II C repeat blocks reveals that they are alpha-helical, except for a single area of disruption. In the class I molecules, the area of disruption corresponds to the class I-specific mAb binding sites. Importantly, the predicted conformational characteristics of this disruption differs for class I and II molecules. The data suggest that only limited changes in amino acid residues differentiate between class I and II molecules in the C repeat region. Therefore, selective (biological) pressures may have contributed to the evolution of these two classes of molecules.
Bessen
D E
DE
Laboratory of Bacteriology and Immunology, Rockefeller University, New York, New York 10021.
Fischetti
V A
VA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D001666:Binding Sites, Antibody; D002352:Carrier Proteins; D003001:Cloning, Molecular; D015723:Gene Library; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D013297:Streptococcus pyogenes / Q000145:classification* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein