Conservation of protective and nonprotective epitopes in M proteins of group A streptococci.
Carefully controlled hybridization experiments with probes from a cloned serotype 5 M protein (M5) gene (smp5) were performed with DNA isolated from heterologous M types of group A streptococci, and the homologies detected by hybridization were compared with the ability of anti-pepM5 serum to cross-opsonize heterologous M types. As previously reported (J.R. Scott, S.K. Hollingshead, and V.A. Fischetti, Infect. Immun. 52:609-612, 1986), extensive structural homologies exist among the 3' ends of heterologous M protein genes, but there appears to be an increase in sequence variation as one moves towards the 5' ends. However, a clear, predictive correlation between the hybridization patterns and cross-opsonization was not observed. Antibodies raised to a synthetic peptide corresponding to central, conserved sequences adjacent to the C-terminal sides of the pepsin cleavage sites in M5, serotype 6 M protein, and serotype 24 M protein cross-reacted with heterologous acid-extracted M antigens but were not protective and did not bind to intact streptococcal cells, indicating that these epitopes are inaccessible on the intact cell surface. Removal of the N-terminal half of M5, serotype 6 M protein, or serotype 24 M protein by pepsin exposed the conserved epitope on the cell surface. These results suggest that immunoaccessible protective epitopes are confined to the highly variable N-terminal halves of M proteins and that a single, broadly conserved protective M protein epitope does not exist.
Miller
L
L
Department of Microbiology, Medical School, University of Newcastle upon Tyne, England.
Burdett
V
V
Poirier
T P
TP
Gray
L D
LD
Beachey
E H
EH
Kehoe
M A
MA
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins; D003429:Cross Reactions; D000939:Epitopes; D005796:Genes; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D013297:Streptococcus pyogenes / Q000276:immunology*; D013329:Structure-Activity Relationship
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000939:Epitopes; C014689:streptococcal M protein