Mapping the immunodeterminants of the complete streptococcal M6 protein molecule. Identification of an immunodominant region.
The immune response to the complete streptococcal M6 protein was examined by kinetic ELISA to determine the reactivity of rabbit and human sera to M6 peptides representing 82% of the native molecule. The results revealed that rabbits immunized with purified native M6 protein or whole streptococci responded by reacting early and predominantly to one of the three sequence repeat regions of the molecule, the B-repeat, antibodies which have been shown to be non-opsonic. Antibodies to peptides representing the hypervariable N-terminal and adjacent A-repeat regions appear when opsonic antibodies are detected in the serum. Antibodies to peptides located within the conserved C-terminal half of the molecule (proximal to the cell) were restricted even after several immunizations. An examination of human sera from individuals with no recent streptococcal infection (greater than 3 yr), revealed that those sera opsonic for M6 streptococci contained antibodies reactive predominantly to the N-terminal and A-repeat regions, supporting the view that opsonic antibodies are long lived. Nonopsonic human sera to M6 streptococci exhibited a low reactivity to all peptides. However, by Western blot analysis, all human sera tested contained antibodies to the conserved region of the molecule, whereas only sera opsonic for M6 streptococci reacted with the variable region. Evidence is presented supporting the view that antibodies to the conserved regions of the M molecule may be conformation dependent.
Fischetti
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VA
Rockefeller University, New York 10021.
Windels
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M
D000595:Amino Acid Sequence; D000818:Animals; D000937:Antigen-Antibody Reactions; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000032:analysis / Q000276:immunology*; D015153:Blotting, Western; D002352:Carrier Proteins; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D007106:Immune Sera; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D010449:Peptide Mapping; D011817:Rabbits; D013329:Structure-Activity Relationship
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000939:Epitopes; D007106:Immune Sera; D010446:Peptide Fragments; C014689:streptococcal M protein