Chapter 7 : Peptide Mimicry of Streptococcal Group A Carbohydrate

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This chapter explores the immunochemical relationships, as defined by antibodies, between the cell wall polysaccharide of (group A streptococci) and peptides. It provides basic information on the structure and immunobiology of the streptococcal cell wall polysaccharide (group A carbohydrate [GAC]). Following comments on the nature of molecular mimicry in general, an overview of prior studies on the cross-reactions between GAC and epitopes on host structures is provided. The next two sections review studies of antibody cross-reactivity between GAC and peptides either that correspond in amino acid sequence to host proteins or that are derived from combinatorial peptide libraries. Molecular analysis of human monoclonal antibodies cross-reactive with -acetyl-β-D-glucosamine (GlcNAc) and peptides revealed that they used a variety of variable-region genes and exhibited little evidence of antigen-driven somatic mutations. It remains unknown if GlcNAc-specific antibodies are pathogenic and, if so, what structural features predispose the antibodies to pathogenicity. Researchers used the phage-display approach to investigate peptide mimicry of GAC with respect to five GAC-specific monoclonal antibodies, including the murine monoclonal antibody HGAC 39.G3. This antibody (IgG3, kappa chain) was generated with the group A vaccine (GAV; heat-killed, pepsin-treated ) as the immunogen and has specificity for the GlcNAc residues of group A carbohydrate.

Citation: Greenspan N, Pinilla C, Shikhman A. 2000. Peptide Mimicry of Streptococcal Group A Carbohydrate, p 83-94. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch7
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Figure 1

Molecular structures of Ac-yryygl-NH (molecular weight, 876; top) and GlcNAc (molecular weight, 221; bottom).

Citation: Greenspan N, Pinilla C, Shikhman A. 2000. Peptide Mimicry of Streptococcal Group A Carbohydrate, p 83-94. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch7
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1. Adderson, E. E.,, A. R. Shikhman,, K. E. Ward,, and M. W. Cunningham. 1998. Molecular analysis of polyreactive monoclonal antibodies from rheumatic carditis: human anti-N-acetylglucosamine/anti-myosin antibody V region genes. J. Immunol. 161: 2020 2031.
2. Appleton, R. S.,, B. E. Victorica,, D. Tamer,, and E. M. Ayoub. 1985. Specificity of persistence of antibody to the streptococcal group A carbohydrate in rheumatic valvular heart disease. J. Lab. Clin. Med. 105: 114 119.
3. Araj, G. F.,, H. A. Majeed,, A. M. Yousof,, and E. M. Ayoub. 1988. Immunoglobulin isotype response to the group-A streptococcal carbohydrate in humans. Acta Pathol. Microbiol. Immunol. Scand. Suppl. 3: 8 12.
4. Ayoub, E. M., 1996. Rheumatic fever, p. 1134 1144. In R. R. Rich,, T. A. Fleisher,, B. D. Schwartz,, W. T. Shearer,, and W. Strober (ed.). Clinical Immunology: Principles and Practice. Mosby-Year Book, Inc., St. Louis, Mo.
5. Catanzaro, F. J.,, C. A. Stetson,, A. J. Morris,, R. Chamovitz,, C. H. Rammelkamp Jr.,, B. L. Stolzer,, and W. D. Perry. 1954. The role of the streptococcus in the pathogenesis of rheumatic fever. Am. J. Med. 17: 749 756.
6. Coligan, J. E.,, T. J. Kindt,, and R. M. Krause. 1978. Structure of the streptococcal groups A, A-variant and C carbohydrates. Immunochemistry 15: 755 760.
7. Cunningham, M. W.,, and S. M. Russell. 1983. Study of heart-reactive antibody in anti-sera and hybridoma culture fluids against group A streptococci. Infect. Immun. 42: 531 538.
8. Dale, J. B.,, and E. H. Beachey. 1982. Protective antigenic determinant of streptococcal M protein shared with sarcolemmal membrane protein of human heart. J. Exp. Med. 156: 1165 1176.
9. Dudding, B. A.,, and E. M. Ayoub. 1968. Persistence of streptococcal group A antibody in patients with rheumatic valvular disease. J. Exp. Med. 128: 1081 1098.
10. Emmrich, F.,, B. Schilling,, and K. Eichmann. 1985. Human immune response to group A streptococcal carbohydrate (A-CHO). I. Quantitative and qualitative analysis of the A-CHO-specific B cell population responding in vitro to polyclonal and specific activation. J. Exp. Med. 161: 547 562.
11. Evavold, B. D.,, and P. M. Allen. 1991. Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science 252: 1308 1310.
12. Geysen, H. M.,, S. J. Rodda,, and T. J. Mason. 1986. A priori delineation of a peptide which mimics a discontinuous antigenic determinant. Mol. Immunol. 23: 709 715.
13. Goldstein, I.,, B. Halpern,, and L. Robert. 1967. Immunological relationship between streptococcus A polysaccharide and the structural glycoproteins of heart valve. Nature 213: 44 47.
14. Goldstein, I.,, L. Scebat,, J. Renais,, P. Hadjinsky,, and J. Dutartre. 1983. Rheumatic-like carditis induced in rabbits by cross-reacting antigens: streptococcus A polysaccharide and rabbit aortic glycoproteins. Isr. J. Med. Sci. 19: 483 90.
15. Greenspan, N. S., 1992. Antigen mimicry with anti-idiotypic antibodies, p. 55 79. In. M. H. V. Van Regen-mortel (ed.), Structure of Antigens, vol. I. CRC Press, Inc., Boca Raton, Fla.
16. Greenspan, N. S.,, W. J. Monafo,, and J. M. Davie. 1987. Interaction of IgG3 anti-streptococcal group A carbohydrate (GAC) antibody with streptococcal group A vaccine: enhancing and inhibiting effects of anti-GAC, anti-isotypic, and anti-idiotypic antibodies. J. Immunol. 138: 285 292.
17. Harris, S. L.,, L. Craig,, J. S. Mehroke,, M. Rashed,, M. B. Zwick,, K. Kenar,, E. J. Toone,, N. Greenspan N.,, F. I. Auzanneau,, J. R. Marino-Albernas,, B. M. Pinto,, and J. K. Scott 1997. Exploring the basis of peptide-carbohydrate cross-reactivity: evidence for discrimination by peptides between closely related anti-carbohydrate antibodies. Proc. Natl. Acad. Sci. USA 94: 2454 2459.
18. Hoess, R.,, U. Brinkmann,, T. Handel,, and I. Pastan. 1993. Identification of a peptide which binds to the carbohydrate-specific monoclonal antibody B3. Gene 128: 43 49.
19. Houghten, R. A.,, C. Pinilla,, S. E. Blondelle,, J. R. Appel,, C. T. Dooley,, and J. H. Cuervo. 1991. Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery. Nature 354: 84 86.
20. Hua, Q. X.,, S. E. Shoelson,, M. Kochoyan,, and M. A. Weiss. 1991. Receptor binding redefined by a structural switch in a mutant human insulin. Nature 354: 238 241.
21. Kaplan, M. H. 1963. 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. 90: 595 606.
22. Kaplan, M. H. 1964. Immunologic relations of streptococcal and tissue antigens. III. Presence in human sera of streptococcal antibody cross-reactive with heart tissue. Association with streptococcal infection, rheumatic fever, and glomerulonephritis. J. Exp. Med. 119: 651 666.
23. Kaplan, M. H.,, and H. Meyersian. 1962. An immunologic cross-reaction between group A streptococcal cells and human heart. Lancet ii: 706 710.
24. Kaplan, M. H.,, and K. H. Svec. 1964. Immunologic relation of streptococcal and tissue antigens. III. Presence in human sera of streptococcal antibody cross-reactive with heart tissue. Association with stretococcal infection, rheumatic fever, and glomerulonephritis. J. Exp. Med. 119: 651 666.
25. Kaplan, M. H.,, R. Bolande,, L. Rakita,, and J. Blair. 1964. Presence of bound immunoglobulins and complement in the myocardium in acute rheumatic fever. N. Engl. J. Med. 271: 637 645.
26. Keitel, T.,, A. Kramer,, H. Wessner,, C. Scholz,, J. Schneider-Mergener,, and W. Hohne. 1997. Crystallographic analysis of anti-p24 (HIV-1) monoclonal antibody cross-reactivity and polyspecificity. Cell 91: 811 820.
27. Kramer, A.,, T. Keitel,, K. Winkler,, W. Stocklein,, W. Hohne,, and J. Schneider-Mergener. 1997. Molecular basis for the binding promiscuity of an anti-p24 (HIV-1) monoclonal antibody. Cell 91: 799 809.
28. Krisher, K.,, and M. W. Cunningham. 1985. Myosin: a link between streptococci and heart. Science 227: 413 415.
29. Lam, K. S.,, S. E. Salmon,, E. M. Hersh,, V. J. Hruby,, W. M. Kazmierski,, and R. J. Knapp. 1991. A new type of synthetic peptide library for identifying ligand-binding activity. Nature 354: 82 84.
30. Lancefield, R. C. 1962. Current knowledge of type-specific M antigens of group A streptococci. J. Immunol. 89: 307 313.
31. Lyampert, L. M.,, L. V. Beletskaya,, N. A. Borodiyuk,, E. V. Gnezditskaya,, L. L. Rassokhina,, and T. A. Danilov. 1976. A cross-reactive antigen of thymus and skin epithelial cells common with the polysaccharide of group A streptococci. Immunology 31: 47 55.
32. McCarty, M. 1956. Variation in the group-specific carbohydrate of group A streptococci. II. Studies on the chemical basis for serological specificity of carbohydrates. J. Exp. Med. 104: 629 643.
33. Morell, A.,, G. Vassalli,, G. G. DeLange,, F. Skvaril,, D. M. Ambrosino,, and G. R. Siber. 1989. Ig allotype-linked regulation of class and subclass composition of natural antibodies to group A streptococcal carbohydrate. J. Immunol. 142: 2495 2500.
34. Pinilla, C.,, J. R. Appel,, G. D. Campbell,, J. Buencamino,, N. Benkirane,, S. Muller,, and N. S. Greenspan. 1998. All-D; peptides recognized by an anti-carbohydrate antibody identified from a positional scanning library. J. Mol. Biol. 283: 1013 1025.
35. Rantakokko, K.,, M. Rimpilainen,, J. Uksila,, C. Jansen,, R. Luukkainen,, and P. Toivanen. 1997. Antibodies to streptococcal cell wall in psoriatic arthritis and cutaneous psoriasis. Clin. Exp. Rheumatol. 15: 399 404.
36. Razon Veronesi, S. 1983. Antipolysaccharide group-specific antibodies of Streptococcus pyogenes in children. Boll. 1st. Sieroter Milan 62: 433 444.
37. Rini, J. M.,, U. Schulze-Gahmen,, and I. A. Wilson. 1992. Structural evidence for induced fit as a mechanism for antibody-antigen recognition. Science 255: 959 965.
38. Salvadori, L. G.,, M. S. Blake,, M. McCarthy,, J. Y. Tai,, and J. B. Zabriskie. 1995. Group A streptococcus-liposome ELISA antibody titers to group A polysaccharide and opsonophagocytic capabilities of the antibodies. J. Infect. Dis. 171: 593 600.
39. Scott, J. K.,, and G. P. Smith. 1990. Searching for peptide ligands with an epitope library. Science 249: 386 390.
40. Shackelford, P. G.,, S. J. Nelson,, A. T. Palma,, and M. H. Nahm. 1988. Human antibodies to group A streptococcal carbohydrate. Ontogeny, subclass restriction, and clonal diversity. J. Immunol. 140: 3200 3205.
41. Sharif, M.,, L. S. Wilkinson,, J. Edwards,, and G. A. Rook. 1989. Membrane N-acetylglucosamine: expression by cells in rheumatoid synovial fluid, and by pre-cultured monocytes. Br. J. Exp. Pathol. 70: 567 577.
42. Sharif, M.,, G. Rook,, L. S. Wilkinson,, J. G. Worrall,, and J. C. W. Edwards. 1990. Terminal N-acetyl-glucosamine in chronic synovitis. Br. J. Rheumatol. 29: 25 31.
43. Shikhman, A. R.,, E. P. Savl'ev,, L. V. Nikolaeva,, V. L. Cherkasov,, and G. I. Anokhina. 1986. Determination of antibodies against ribosomes and cell wall components, detection of circulating antigens of group A streptococcus in patients with erysipelas. Zh. Microbiol. Epidemiol. Immunobiol. December: 91 95.
44. Shikhman, A. R.,, N. S. Greenspan,, and M. W. Cunningham. 1993. A subset of mouse monoclonal antibodies crossreactive with cytoskeletal proteins and group A streptococcal M proteins recognizes N-acetyl-β-D;-glucosamine. J. Immunol. 151: 3902 3913.
45. Shikhman, A. R.,, and M. W. Cunningham. 1994. Immunological mimicry between N-acetyl-beta-D;-glucosamine and cytokeratin peptides. Evidence for a microbially driven antikeratin antibody response. J. Immunol. 152: 4375 4387.
46. Shikhman, A. R.,, N. S. Greenspan,, and M. W. Cunningham. 1994. Cytokeratin peptide SFGSFGGGY mimics N-acetyl-β-D;-glucosamine in reaction with antibodies and lectins, and induces in vivo anti-carbohydrate antibody response. J. Immunol. 153: 5593 5606.
47. Tran Van Nhieu, G.,, and R. R. Isberg. 1993. Bacterial internalization mediated by β 1 chain integrins is determined by ligand affinity and receptor density. EMBO J. 12: 1887 1895.
48. Turner, J. R.,, A. M. Tartakoff,, and N. S. Greenspan. 1990. Cytologic assessment of nuclear and cytoplasmic O-linked N-acetyl-glucosamine distribution by using anti-streptococcal monoclonal antibodies. Proc. Natl. Acad. Sci. USA 87: 5608 5612.
49. van de Rjjn, I.,, J. B. Zabriskie,, and M. McCarty. 1977. Group A streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen. J. Exp. Med. 146: 579 599.
50. Williams, R. C. Jr., 1985. Molecular mimicry and rheumatic fever. Clin. Rheum. Dis. 11: 573 590.
51. Wilson, I. A.,, and R. L. Stanfield. 1994. Antibody-antigen interactions: new structures and new conformational changes. Curr. Opin. Struct. Biol. 4: 857 867.
52. Zabriskie, J. B.,, and E. H. Freimer. 1966. An immunological relationship between the group A streptococcus and mammalian muscle. J. Exp. Med. 124: 661 678.
53. Zabriskie, J. B.,, K. C. Hsu,, and B. C. Seegal. 1970. Heart-reactive antibody associated with rheumatic fever: characterization and diagnostic significance. Clin. Exp. Immunol. 7: 147 159.


Generic image for table
Table 1

Relative affinities for analogs of Ac-yryygl-NH recognized by monoclonal antibody HGAC 39.G3

Citation: Greenspan N, Pinilla C, Shikhman A. 2000. Peptide Mimicry of Streptococcal Group A Carbohydrate, p 83-94. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch7

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