Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Jun;85(12):4516–4520. doi: 10.1073/pnas.85.12.4516

Renal autoimmune epitope of group A streptococci specified by M protein tetrapeptide Ile-Arg-Leu-Arg.

W Kraus 1, E H Beachey 1
PMCID: PMC280461  PMID: 2454473

Abstract

The renal glomerular cross-reactivity of the amino-terminal region of type 1 streptococcal M protein was investigated. Antisera raised in rabbits against a synthetic peptide representing residues 1-26 and a peptide from which residues 20-22 had been omitted during synthesis were capable not only of opsonizing type 1 streptococci but also of reacting in immunofluorescence tests with human renal glomeruli. The cross-reactions were completely inhibited by the immunizing peptides. By using additional synthetic peptides in these inhibition studies, the glomerular cross-reactive epitope was localized to a tetrapeptide sequence Ile-Arg-Leu-Arg at positions 23-26. A number of synthetic M1 peptides containing the tetrapeptide sequence were inhibitory, whereas the M1 peptides lacking the sequence or unrelated tetrapeptides Arg-Gly-Asp-Ser or Arg-Gly-Phe-Ser were without effect. Furthermore, Ile-Arg-Leu-Arg affinity-purified antibodies reacted with renal glomeruli, and the reactivity was inhibited by the tetrapeptide as well as by type 1 M protein. These results indicate that a renal glomerular autoimmune epitope resides in a tetrapeptide Ile-Arg-Leu-Arg near the amino terminus of type 1 streptococcal M protein.

Full text

PDF
4517

Images in this article

4518Image
on p.4518

Selected References

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

  1. Beachey E. H., Gras-Masse H., Tarter A., Jolivet M., Audibert F., Chedid L., Seyer J. M. Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem. J Exp Med. 1986 Jun 1;163(6):1451–1458. doi: 10.1084/jem.163.6.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Beachey E. H., Seyer J. M., Dale J. B. Protective immunogenicity and T lymphocyte specificity of a trivalent hybrid peptide containing NH2-terminal sequences of types 5, 6, and 24 M proteins synthesized in tandem. J Exp Med. 1987 Sep 1;166(3):647–656. doi: 10.1084/jem.166.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. Beachey E. H., Tartar A., Seyer J. M., Chedid L. Epitope-specific protective immunogenicity of chemically synthesized 13-, 18-, and 23-residue peptide fragments of streptococcal M protein. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2203–2207. doi: 10.1073/pnas.81.7.2203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Berrios X., Quesney F., Morales A., Blazquez J., Lagomarsino E., Bisno A. L. Acute rheumatic fever and poststreptococcal glomerulonephritis in an open population: comparative studies of epidemiology and bacteriology. J Lab Clin Med. 1986 Dec;108(6):535–542. [PubMed] [Google Scholar]
  9. COONS A. H., KAPLAN M. H. Localization of antigen in tissue cells; improvements in a method for the detection of antigen by means of fluorescent antibody. J Exp Med. 1950 Jan 1;91(1):1–13. doi: 10.1084/jem.91.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. Edman P., Begg G. A protein sequenator. Eur J Biochem. 1967 Mar;1(1):80–91. doi: 10.1007/978-3-662-25813-2_14. [DOI] [PubMed] [Google Scholar]
  17. Fillit H., Damle S. P., Gregory J. D., Volin C., Poon-King T., Zabriskie J. Sera from patients with poststreptococcal glomerulonephritis contain antibodies to glomerular heparan sulfate proteoglycan. J Exp Med. 1985 Feb 1;161(2):277–289. doi: 10.1084/jem.161.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fitzsimons E. J., Jr, Weber M., Lange C. F. The isolation of cross-reactive monoclonal antibodies: hybridomas to streptococcal antigens cross-reactive with mammalian basement membrane. Hybridoma. 1987 Feb;6(1):61–69. doi: 10.1089/hyb.1987.6.61. [DOI] [PubMed] [Google Scholar]
  19. Goroncy-Bermes P., Dale J. B., Beachey E. H., Opferkuch W. Monoclonal antibody to human renal glomeruli cross-reacts with streptococcal M protein. Infect Immun. 1987 Oct;55(10):2416–2419. doi: 10.1128/iai.55.10.2416-2419.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. KAPLAN M. H. IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS. I. PROPERTIES OF AN ANTIGEN IN CERTAIN STRAINS OF GROUP A STREPTOCOCCI EXHIBITING AN IMMUNOLOGIC CROSS-REACTION WITH HUMAN HEART TISSUE. J Immunol. 1963 Apr;90:595–606. [PubMed] [Google Scholar]
  22. Kefalides N. A., Pegg M. T., Ohno N., Poon-King T., Zabriskie J., Fillit H. Antibodies to basement membrane collagen and to laminin are present in sera from patients with poststreptococcal glomerulonephritis. J Exp Med. 1986 Mar 1;163(3):588–602. doi: 10.1084/jem.163.3.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Khandke K. M., Fairwell T., Manjula B. N. Difference in the structural features of streptococcal M proteins from nephritogenic and rheumatogenic serotypes. J Exp Med. 1987 Jul 1;166(1):151–162. doi: 10.1084/jem.166.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kraus W., Haanes-Fritz E., Cleary P. P., Seyer J. M., Dale J. B., Beachey E. H. Sequence and type-specific immunogenicity of the amino-terminal region of type 1 streptococcal M protein. J Immunol. 1987 Nov 1;139(9):3084–3090. [PubMed] [Google Scholar]
  25. Krisher K., Cunningham M. W. Myosin: a link between streptococci and heart. Science. 1985 Jan 25;227(4685):413–415. doi: 10.1126/science.2578225. [DOI] [PubMed] [Google Scholar]
  26. LANCEFIELD R. C. Current knowledge of type-specific M antigens of group A streptococci. J Immunol. 1962 Sep;89:307–313. [PubMed] [Google Scholar]
  27. 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]
  28. Mouw A. R., Beachey E. H., Burdett V. Molecular evolution of streptococcal M protein: cloning and nucleotide sequence of the type 24 M protein gene and relation to other genes of Streptococcus pyogenes. J Bacteriol. 1988 Feb;170(2):676–684. doi: 10.1128/jb.170.2.676-684.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Rothbard J. B., Fernandez R., Schoolnik G. K. Strain-specific and common epitopes of gonococcal pili. J Exp Med. 1984 Jul 1;160(1):208–221. doi: 10.1084/jem.160.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Swanson J., Hsu K. C., Gotschlich E. C. Electron microscopic studies on streptococci. I. M antigen. J Exp Med. 1969 Nov 1;130(5):1063–1091. doi: 10.1084/jem.130.5.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yoshitake S., Yamada Y., Ishikawa E., Masseyeff R. Conjugation of glucose oxidase from Aspergillus niger and rabbit antibodies using N-hydroxysuccinimide ester of N-(4-carboxycyclohexylmethyl)-maleimide. Eur J Biochem. 1979 Nov;101(2):395–399. doi: 10.1111/j.1432-1033.1979.tb19731.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES