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. 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.

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Selected References

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  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]

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