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. 1988 Jun 1;167(6):1849–1859. doi: 10.1084/jem.167.6.1849

Protective and heart-crossreactive epitopes located within the NH2 terminus of type 19 streptococcal M protein

PMCID: PMC2189697  PMID: 2455015

Abstract

M protein was purified to homogeneity from limited pepsin digests of intact type 19 streptococci (pep M19). The purified pep M19 when emulsified in CFA and injected into rabbits evoked type-specific and crossreactive opsonic antibodies, as well as heart-crossreactive antibodies. The NH2-terminal primary structure of pep M19 was determined and a peptide copying the first 24 amino acids [SM19(1-24)C] was chemically synthesized. Rabbits that were immunized with the unconjugated peptide developed antibodies that recognized the native pep M19, as determined by ELISA, and opsonic antibodies against type 19 streptococci, as determined by in vitro opsonophagocytosis tests. The synthetic peptide also evoked antibodies that crossreacted with a 60-kD sarcolemmal membrane protein of human myocardium. By using overlapping synthetic subpeptides as immunoinhibitors, the opsonic and heart- crossreactive epitopes of SM19(1-24)C were localized to SM19(11-24)C. Our data confirm the presence of heart-crossreactive epitopes within the primary structure of pep M19 and show that these potentially harmful autoimmune epitopes may be located in the NH2-terminal regions of certain M proteins. We conclude that continued efforts to identify the primary structures of protective and heart-crossreactive epitopes will be necessary to elucidate the pathogenesis of acute rheumatic heart disease and to develop safe and effective streptococcal vaccines.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beachey E. H., Seyer J. M., Dale J. B., Hasty D. L. Repeating covalent structure and protective immunogenicity of native and synthetic polypeptide fragments of type 24 streptococcal M protein. Mapping of protective and nonprotective epitopes with monoclonal antibodies. J Biol Chem. 1983 Nov 10;258(21):13250–13257. [PubMed] [Google Scholar]
  2. Beachey E. H., Seyer J. M., Dale J. B., Simpson W. A., Kang A. H. Type-specific protective immunity evoked by synthetic peptide of Streptococcus pyogenes M protein. Nature. 1981 Jul 30;292(5822):457–459. doi: 10.1038/292457a0. [DOI] [PubMed] [Google Scholar]
  3. Beachey E. H., Seyer J. M., Kang A. H. Primary structure of protective antigens of type 24 streptococcal M protein. J Biol Chem. 1980 Jul 10;255(13):6284–6289. [PubMed] [Google Scholar]
  4. Beachey E. H., Seyer J. M. Protective and nonprotective epitopes of chemically synthesized peptides of the NH2-terminal region of type 6 streptococcal M protein. J Immunol. 1986 Mar 15;136(6):2287–2292. [PubMed] [Google Scholar]
  5. Beachey E. H., Stollerman G. H., Chiang E. Y., Chiang T. M., Seyer J. M., Kang A. H. Purification and properties of M protein extracted from group A streptococci with pepsin: covalent structure of the amino terminal region of type 24 M antigen. J Exp Med. 1977 Jun 1;145(6):1469–1483. doi: 10.1084/jem.145.6.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chou P. Y., Fasman G. D. Prediction of protein conformation. Biochemistry. 1974 Jan 15;13(2):222–245. doi: 10.1021/bi00699a002. [DOI] [PubMed] [Google Scholar]
  7. Dale J. B., Beachey E. H. Epitopes of streptococcal M proteins shared with cardiac myosin. J Exp Med. 1985 Aug 1;162(2):583–591. doi: 10.1084/jem.162.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dale J. B., Beachey E. H. Localization of protective epitopes of the amino terminus of type 5 streptococcal M protein. J Exp Med. 1986 May 1;163(5):1191–1202. doi: 10.1084/jem.163.5.1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dale J. B., Beachey E. H. Multiple, heart-cross-reactive epitopes of streptococcal M proteins. J Exp Med. 1985 Jan 1;161(1):113–122. doi: 10.1084/jem.161.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dale J. B., Beachey E. H. Protective antibody against a peptide fragment of type 5 streptococcal M protein cross-reacts with human heart tissue. Trans Assoc Am Physicians. 1982;95:286–291. [PubMed] [Google Scholar]
  11. Dale J. B., Beachey E. H. Protective antigenic determinant of streptococcal M protein shared with sarcolemmal membrane protein of human heart. J Exp Med. 1982 Oct 1;156(4):1165–1176. doi: 10.1084/jem.156.4.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dale J. B., Beachey E. H. Sequence of myosin-crossreactive epitopes of streptococcal M protein. J Exp Med. 1986 Nov 1;164(5):1785–1790. doi: 10.1084/jem.164.5.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dale J. B., Ofek I., Beachey E. H. Heterogeneity of type-specific and cross-reactive antigenic determinants within a single M protein of group A streptococci. J Exp Med. 1980 May 1;151(5):1026–1038. doi: 10.1084/jem.151.5.1026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dale J. B., Seyer J. M., Beachey E. H. Type-specific immunogenicity of a chemically synthesized peptide fragment of type 5 streptococcal M protein. J Exp Med. 1983 Nov 1;158(5):1727–1732. doi: 10.1084/jem.158.5.1727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hollingshead S. K., Fischetti V. A., Scott J. R. Complete nucleotide sequence of type 6 M protein of the group A Streptococcus. Repetitive structure and membrane anchor. J Biol Chem. 1986 Feb 5;261(4):1677–1686. [PubMed] [Google Scholar]
  16. Jones K. F., Manjula B. N., Johnston K. H., Hollingshead S. K., Scott J. R., Fischetti V. A. Location of variable and conserved epitopes among the multiple serotypes of streptococcal M protein. J Exp Med. 1985 Mar 1;161(3):623–628. doi: 10.1084/jem.161.3.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. LANCEFIELD R. C. Current knowledge of type-specific M antigens of group A streptococci. J Immunol. 1962 Sep;89:307–313. [PubMed] [Google Scholar]
  18. Manjula B. N., Acharya A. S., Fairwell T., Fischetti V. A. Antigenic domains of the streptococcal Pep M5 protein. Localization of epitopes crossreactive with type 6 M protein and identification of a hypervariable region of the M molecule. J Exp Med. 1986 Jan 1;163(1):129–138. doi: 10.1084/jem.163.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Manjula B. N., Acharya A. S., Mische S. M., Fairwell T., Fischetti V. A. The complete amino acid sequence of a biologically active 197-residue fragment of M protein isolated from type 5 group A streptococci. J Biol Chem. 1984 Mar 25;259(6):3686–3693. [PubMed] [Google Scholar]
  20. Manjula B. N., Trus B. L., Fischetti V. A. Presence of two distinct regions in the coiled-coil structure of the streptococcal Pep M5 protein: relationship to mammalian coiled-coil proteins and implications to its biological properties. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1064–1068. doi: 10.1073/pnas.82.4.1064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Phillips G. N., Jr, Flicker P. F., Cohen C., Manjula B. N., Fischetti V. A. Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4689–4693. doi: 10.1073/pnas.78.8.4689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sargent S. J., Beachey E. H., Corbett C. E., Dale J. B. Sequence of protective epitopes of streptococcal M proteins shared with cardiac sarcolemmal membranes. J Immunol. 1987 Aug 15;139(4):1285–1290. [PubMed] [Google Scholar]
  23. Scott J. R., Pulliam W. M., Hollingshead S. K., Fischetti V. A. Relationship of M protein genes in group A streptococci. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1822–1826. doi: 10.1073/pnas.82.6.1822. [DOI] [PMC free article] [PubMed] [Google Scholar]

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