Spontaneous M6 protein size mutants of group A streptococci display variation in antigenic and opsonogenic epitopes.
Deletions of highly, but not entirely, homologous intragenic sequence repeats result in amino acid sequence and conformational changes in the M proteins of spontaneous M protein-size variants of group A streptococci. To determine if antigenic changes occurred as a result of these deletion mutations, monoclonal and polyclonal antibodies with defined epitopes were used in competition assays. Competing antigens were either purified pepsin-derived fragments (representing the amino-terminal half of the molecule) of parent and mutant M proteins or were intact bacterial cells. These assays showed that antigenic variation occurred at the site(s) of these deletions but not at adjacent or distant epitopes. Once cleaved from the bacterium by pepsin, the M molecules also underwent conformational changes, which were reflected in their ability to compete. A monoclonal antibody opsonic for M6 streptococci lost its ability to completely opsonize one of the size mutants in this study. Therefore, spontaneous intragenic events between repeats within emm-6, the structural gene for the M6 protein, do result in structural variations within the mutant M molecules. This variation alters the ability of certain antibodies, originally produced in response to sequences in the parental M molecule, to bind to the mutant M molecules or opsonize the mutant organisms. Group A streptococci have evolved a mechanism for generating antigenic diversity that differs from currently known mechanisms in other bacterial species.
Jones
K F
KF
Laboratory of Bacteriology and Immunology, Rockefeller University, New York, NY 10021.
Hollingshead
S K
SK
Scott
J R
JR
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* / Q000276:immunology; D002352:Carrier Proteins; D002872:Chromosome Deletion; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis* / Q000235:genetics; D005796:Genes; D008969:Molecular Sequence Data; D009895:Opsonin Proteins / Q000032:analysis*; D011487:Protein Conformation; D013297:Streptococcus pyogenes / Q000235:genetics*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000939:Epitopes; D009895:Opsonin Proteins; C014689:streptococcal M protein