Human antibodies to the conserved region of the M protein: opsonization of heterologous strains of group A streptococci.
A 20-mer peptide (p145) in the carboxyl-terminal region of the M protein of group A streptococci (GAS) has previously been defined as the target of bactericidal antibodies. Sequence analysis of seven field isolates from indigenous Australians living in an area highly endemic for GAS and five laboratory reference strains (encompassing nine unique serotypes plus three nontypeables) demonstrates that this region is highly conserved (sequence identity ranging from 65 to 95%) with six of the 12 sequences being identical to p145. Most of the sequence dissimilarity is contained within the last seven amino acids of p145. Competitive ELISA demonstrates that human antibodies specific for p145 cannot discriminate between p145 and synthetic peptides representing four from four of the variant sequences tested. Ig purified from endemic sera was able to opsonize each of the GAS isolates and free p145 as well as a peptide expressing a minimal conformational epitope within p145 (requiring amino acids between positions 2 and 13 of p145), but not an irrelevant peptide, were able to partially or completely inhibit opsonization of all isolates and reference strains. Thus adult endemic sera contain antibodies which are bactericidal for multiple GAS serotypes and which are specific for a sequence of 12 amino acids contained within the p145 region of the M protein.
Brandt
E R
ER
Molecular Immunology Laboratory, Queensland Institute of Medical Research, Australia.
Hayman
W A
WA
Currie
B
B
Pruksakorn
S
S
Good
M F
MF
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins; D017124:Conserved Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000939:Epitopes; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; C082264:Pom121 protein, rat; C014689:streptococcal M protein; D004247:DNA