Chapter 1 : The Streptococcal Superantigens

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

The Streptococcal Superantigens, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815844/9781555814243_Chap01-1.gif /docserver/preview/fulltext/10.1128/9781555815844/9781555814243_Chap01-2.gif


Streptococcal toxic shock syndrome (STSS) is caused by a sudden release of one or more streptococcal superantigens (SAgs) into the blood. The conditions that result in this sudden production of toxin remain one of the major questions in the study and treatment of invasive streptococcal disease. The availability of streptococcal genomes has simplified the effort of identifying new SAgs. Minor allelic variation has been found for streptococcal pyrogenic exotoxin (SPE)-A and SPE-C. Two cocrystal structures of streptococcal SAgs bound to soluble TcR reveal how SPE-A interacts with murineVβ8.2 and SPE-C interacts with human Vβ2.1 complexes. Streptococcal SAgs when combined with small doses of endotoxin such as lipopolysaccharide (LPS) are lethal in rabbits. The focus on without knowledge of other more potent streptococcal SAgs such as streptococcal mitogenic exotoxin Z (SMEZ) and SPE-J tends to reduce the significance of these earlier studies by adding the potential for two or more SAgs to contribute to toxicity. Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that affects mostly young children and is now recognized as the leading cause of acquired heart disease in children in the developed world. The streptococcal SAgs are a family of secreted toxins similar to their staphylococcal cousins, but with some unique features, in particular with regard to expression and potency. It is clear that the SAg genes originated in staphylococci, and the fact that most are encoded in mobile phage suggests that they confer a significant advantage to the organism.

Citation: Fraser J, Proft T. 2007. The Streptococcal Superantigens, p 3-20. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch1

Key Concept Ranking

Tumor Necrosis Factor alpha
MHC Class II
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Abe, J.,, J. Forrester,, T. Nakahara,, J. Lafferty,, B. Kotzin, and, D. Leung. 1991. Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B. J. Immunol. 146:37473750.
2. Abe, J.,, B. L. Kotzin,, K. Jujo,, M. E. Melish,, M. P. Glode,et al. 1992. Selective expansion of T cells expressing T-cell receptor variable regions V beta 2 and V beta 8 in Kawasaki disease. Proc. Natl. Acad. Sci. USA 89:40664070.
3. Artiushin, S. C.,, J. F. Timoney,, A. S. Sheoran, and, S. K. Muthupalani. 2002. Characterization and immunogenicity of pyrogenic mitogens SePE-H and SePE-I of Streptococcus equi. Microb. Pathog. 32:7185.
4. Baker, H.,, T. Proft,, P. Webb,, V. Arcus,, J. Fraser, and, E. Baker. 2004. Crystallographic and mutational data show that the streptococcal pyrogenic exotoxin J can use a common binding surface for T cell receptor binding and dimerization. J. Biol. Chem. 279:3857138576.
5. Banks, D.,, B. Lei, and, J. Musser. 2003. Prophage induction and expression of prophage-encoded virulence factors in group A Streptococcus serotype M3 strain MGAS315. Infect. Immun. 71:70797086.
6. Basma, H.,, A. Norrby-Teglund,, Y. Guedez,, A. McGeer,, D. E. Low, et al. 1999. Risk factors in the patho-genesis of invasive group A streptococcal infections: role of protective humoral immunity. Infect. Immun. 67:18711877.
7. Beres, S. B.,, G. L. Sylva,, K. D. Barbian,, B. Lei,, J. S. Hoff, et al. 2002. Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence. Proc. Natl. Acad. Sci. USA 99:1007810083.
8. Bessen, D. E.,, M. W. Izzo,, T. R. Fiorentino,, R. M. Caringal,, S. K. Hollingshead, and, B. Beall. 1999. Genetic linkage of exotoxin alleles and emm gene markers for tissue tropism in group A streptococci. J. Infect. Dis. 179:627636.
9. Bette, M.,, M. K. Schafer,, N. van Rooijen,, E. Weihe, and, B. Fleischer. 1993. Distribution and kinetics of superantigen-induced cytokine gene expression in mouse spleen. J. Exp. Med. 178:15311539.
10. Bohach, G.,, A. Hauser, and, P. Schlievert. 1988. Cloning of the gene, speB, for streptococcal pyrogenic exotoxin type B in Escherichia coli. Infect. Immun. 56:16651667.
11. Braun, M. A.,, D. Gerlach,, U. F. Hartwig,, J. H. Ozegowski,, F. Romagne, et al. 1993. Stimulation of human T cells by streptococcal “superantigen” erythrogenic toxins (scarlet fever toxins). J. Immunol. 150:24572466.
12. Broudy, T. B.,, V. Pancholi, and, V. A. Fischetti. 2001. Induction of lysogenic bacteriophage and phage-associated toxin from group A streptococci during coculture with human pharyngeal cells. Infect. Immun. 69:14401443.
13. Carapetis, J.,, R. Robins-Browne,, D. Martin,, T. Shelby-James, and, G. Hogg. 1995. Increasing severity of invasive group A streptococcal disease in Australia: clinical and molecular epidemiological features and identification of a new virulent M-nontypeable clone. Clin. Infect. Dis. 21:12201227.
14. Cimaz, R., and, F. Falcini. 2003. An update on Kawasaki disease. Autoimmun. Rev. 2:258263.
15. Cunningham, M. 2000. Pathogenesis of group A Streptococcal Infections. Clin. Microbiol. Rev. 13:470511.
16. De Marzi, M. C.,, M. M. Fernandez,, E. J. Sundberg,, L. Molinero,, N. W. Zwirner, et al. 2004. Cloning, expression and interaction of human T-cell receptors with the bacterial superantigen SSA. Eur. J. Biochem. 271:40754083.
17. Dick, G., and, G. Dick. 1983. Landmark article Jan 26, 1924: the etiology of scarlet fever. By George F. Dick and Gladys Henry Dick. JAMA 250:3096.
18. Eriksson, B. K. G.,, J. Andersson,, S. E. Holm, and, M. Norgren. 1999. Invasive Group A Streptococcal infections: T1M1 isolates expressing pyrogenic exotoxins A and B in combination with selective lack of toxin-neutralizing antibodies are associated with increased risk of streptococcal toxic shock syndrome. J. Infect. Dis. 180:410418.
19. Fast, D. J.,, P. M. Schlievert, and, R. D. Nelson. 1989. Toxic shock syndrome-associated staphylococcal and streptococcal pyrogenic toxins are potent inducers of tumor necrosis factor production. Infect. Immun. 57:291294.
20. Ferretti, J. J.,, D. Ajdic, and, W. M. McShan. 2004. Comparative genomics of streptococcal species. Indian J. Med. Res. 119(Suppl):16.
21. Ferretti, J. J.,, W. M. Mcshan,, D. Ajdic,, D. J. Savic,, G. Savic, et al. 2001. Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc. Natl. Acad. Sci. USA 98:46584663.
22. Gerlach, D.,, B. Fleischer,, M. Wagner,, K. Schmidt,, S. Vettermann, and, W. Reichardt. 2000. Purification and biochemical characterization of a basic superantigen (SPEX/SMEZ3) from Streptococcus pyogenes. FEMS Microbiol. Lett. 188:153163.
23. Gerlach, D.,, H. Knoll,, W. Köhler,, J. Ozegowski, and, V. Hribalova. 1983. Isolation and characterization of erythrogenic toxins. V. Communication: identity of erythrogenic toxin type B and streptococcal proteinase precursor. Zentralbl. Bakteriol. Mikrobiol. Hyg. [A] 255:221233.
24. Gerlach, D.,, H. Knoll,, W. Kohler, and, J. H. Ozegowski. 1981. Isolation and characterization of erythrogenic toxins of Streptococcus pyogenes. 3. Communication: comparative studies of type A erythrogenic toxins. Zentralbl. Bakteriol. Mikrobiol. Hyg. [A] 250:277286. (In German.)
25. Gerlach, D.,, W. Reichardt,, B. Fleischer, and, K. Schmidt. 1994. Separation of mitogenic and pyrogenic activities from so-called erythrogenic toxin type B (Streptococcal proteinase). Zentralbl. Bakteriol. 280:507514.
26. Graham, M.,, K. Virtaneva,, S. Porcella,, W. Barry,, B. Gowen, et al. 2005. Group A Streptococcus tran-scriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies. Am. J.Pathol. 166:455465.
27. Green, N. M.,, S. Zhang,, S. F. Porcella,, M. J. Nagiec,, K. D. Barbian, et al. 2005. Genome sequence of a serotype M28 strain of group A streptococcus: potential new insights into puerperal sepsis and bacterial disease specificity. J. Infect. Dis. 192:760770.
28. Hackett, S. P., and, D. L. Stevens. 1992. Streptococcal toxic shock syndrome: synthesis of tumor necrosis factor and interleukin-1 by monocytes stimulated with pyrogenic exotoxin-A and streptolysin-O. J. Infect.Dis. 165:879885.
29. Hauser, A.,, D. Stevens,, E. Kaplan, and, P. Schlievert. 1991. Molecular analysis of pyrogenic exotoxins from Streptococcus pyogenes isolates associated with toxic shock-like syndrome. J. Clin. Microbiol. 29:15621567.
30. Hooker, S., and, E. Follensby. 1934. Studies on scarlet fever. II. Different toxins produced by hemolytic streptococci of scarlatinal origin. J. Immunol. 27:177193.
31. Hsueh, P.,, J. Wu,, P. Tsai,, J. Liu,, Y. Chuang, and, K. Luh. 1998. Invasive group A streptococcal disease in Taiwan is not associated with the presence of streptococcal pyrogenic exotoxin genes. Clin. Infect. Dis. 26:584589.
32. Hudson, K. R.,, R. E. Tiedemann,, R. G. Urban,, S. C. Lowe,, J. L. Strominger, and, J. D. Fraser. 1995. Staphylococcal enterotoxin A has two cooperative binding sites on major histocompatibility complex class II. J. Exp. Med. 182:711720.
33. Ikebe, T.,, A. Wada,, Y. Inagaki,, K. Sugama,, R. Suzuki, et al. 2002. Dissemination of the phage-associated novel superantigen gene speL in recent invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan. Infect. Immun. 70:32273233.
34. Imanishi, K.,, H. Igarashi, and, T. Uchiyama. 1990. Activation of murine T cells by streptococcal pyrogenic exotoxin type A. Requirement for MHC class II molecules on accessory cells and identification of V beta elements in T cell receptor of toxin-reactive T cells. J. Immunol. 145:31703176.
35. Jupin, C.,, S. Anderson,, C. Damais,, J. E. Alouf, and, M. Parant. 1988. Toxic shock syndrome toxin as an in-ducer of human tumor necrosis factors and γ-interferon. J. Exp. Med. 167:752761.
36. Kalia, A.,, M. C. Enright,, B. G. Spratt, and, D. E. Bessen. 2001. Directional gene movement from human-pathogenic to commensal-like streptococci. Infect. Immun. 69:48584869.
37. Kamezawa, Y.,, T. Nakahara,, S. Nakano,, Y. Abe,, J. Nozaki-Renard, and, T. Isono. 1997. Streptococcal mitogenic exotoxin Z, a novel acidic superantigenic toxin produced by a T1 strain of Streptococcus pyogenes. Infect. Immun. 65: 38283833.
38. Kapur, V.,, K. Nelson,, P. M. Schlievert,, R. K. Selander, and, J. M. Musser. 1992. Molecular population genetic evidence of horizontal spread of two alleles of the pyrogenic exotoxin C gene (speC) among pathogenic clones of Streptococcus pyogenes. Infect. Immun. 60:35133517.
39. Kazmi, S. U.,, R. Kansal,, R. K. Aziz,, M. Hooshdaran,, A. Norrby-Teglund, et al. 2001. Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group a streptococcal isolates in vivo. Infect. Immun. 69:49884995.
40. Kim, M. H., and, P. M. Schlievert. 1997. Molecular genetics, structure, and immunobiology of streptococcal pyrogenic exotoxin A and C, p. 257279. In D. Y. M. Leung,, B. T. Huber, and, P. M. Schlievert(ed.), Superantigens. Molecular Biology, Immunobiology and Relevance to Human Disease. Marcel Dekker, New York, N.Y.
41. Kim, Y., and, D. Watson. 1970. A purified group A streptococcal pyrogenic exotoxin. Physiochemical and biological properties, including the enhancement of susceptibility to endotoxin lethal shock. J. Exp. Med. 131:611622.
42. Konishi, N.,, K. Baba,, J. Abe,, T. Maruko,, K. Waki, et al. 1996. A case of Kawasaki disease with coronary artery aneurysms documenting Yersinia pseudotuberculosis infection. Acta Paediatr. 86:661664.
43. Kotb, M.,, A. Norrby-Teglund,, A. McGeer,, H. El-Sherbini,, M. Dorak, et al. 2002. An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections. Nature Med. 8:13981404.
44. Lee, P. K., and, P. M. Schlievert. 1989. Quantification and toxicity of group A streptococcal pyrogenic exotoxins in an animal model of toxic shock syndrome-like illness. J. Clin. Microbiol. 27:18901892.
45. Leonard, B.,, P. Lee,, M. Jenkins, and, P. M. Schlievert. 1991. Cell and receptor requirements for streptococ-cal pyrogenic exotoxin T cell mitogenicity. Infect. Immun. 59:12101214.
46. Li, H.,, A. Llera,, D. Tsuchiya,, L. Leder,, X. Ysern, et al. 1998. Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B. Immunity 9: 807816.
47. Li, P. L.,, R. E. Tiedemann,, S. L. Moffat, and, J. D. Fraser. 1997. The superantigen streptococcal pyrogenic exotoxin C (SPE-C) exhibits a novel mode of action. J. Exp. Med. 186:375383.
48. Li, Y.,, H. Li,, N. Dimasi,, J. K. McCormick,, R. Martin, et al. 2001. Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC Class II. Immunity 14:93104.
49. Llewelyn, M., and, J. Cohen. 2002. Superantigens: microbial agents that corrupt immunity. Lancet Infect. Dis. 2:156162.
50. Llewelyn, M.,, S. Sriskandan,, M. Peakman,, D. Ambrozak,, D. Douek, et al. 2004. HLA class II polymorphisms determine responses to bacterial superantigens. J. Immunol. 172:17191726.
51. McCormick, J.,, A. Pragman,, J. Stolpa,, D. Leung, and, P. Schlievert. 2001. Functional characterization of streptococcal pyrogenic exotoxin J, a novel superantigen. Infect. Immun. 69:13811388.
52. McCormick, J. K.,, J. M. Yarwood, and, P. M. Schlievert. 2001. Toxic shock syndrome and bacterial super-antigens: an update. Annu. Rev. Microbiol. 55:77104.
53. McDonald, M.,, B. Currie, and, J. Carapetis. 2004. Acute rheumatic fever: a chink in the chain that links the heart to the throat? Lancet Infect. Dis. 4:240245.
54. Miethke, T.,, C. Wahl,, K. Heeg,, B. Echtenacher,, P. H. Krammer, and, H. Wagner. 1992. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J. Exp. Med. 175:9198.
55. Miyoshi-Akiyama, T.,, J. Zhao,, H. Kato,, K. Kikuchi,, K. Totsuka,, Y. Kataoka,, M. Katsumi, and, T. Uchiyama. 2003. Streptococcus dysgalactiae-derived mitogen (SDM), a novel bacterial superantigen: characterization of its biological activity and predicted tertiary structure. Mol. Microbiol. 47:15891599.
56. Mollick, J. A.,, G. G. Miller,, J. M. Musser,, R. G. Cook,, D. Grossman, and, R. R. Rich. 1993. A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C. J. Clin. Invest. 92:710719.
57. Mueller-Alouf, H.,, J. E. Alouf,, D. Gerlach,, J. H. Ozegowski,, C. Fitting, and, J. M. Cavaillon. 1996. Human pro- and anti-inflammatory cytokine patterns induced by Streptococcus pyogenes erythrogenic (pyro-genic) exotoxins A and C superantigens. Infect. Immun. 64:14501453.
58. Muller-Alouf, H.,, T. Proft,, T. M. Zollner,, D. Gerlach,, E. Champagne, et al. 2001. Pyrogenicity and cytokine-inducing properties of Streptococcus pyogenes superantigens: comparative study of streptococ-cal mitogenic exotoxin Z and pyrogenic exotoxin A. Infect. Immun. 69:41414145.
59. Nakagawa, I.,, K. Kurokawa,, A. Yamashita,, M. Nakata,, Y. Tomiyasu, et al. 2003. Genome sequence of an M3 strain of Streptococcus pyogenes reveals a large-scale genomic rearrangement in invasive strains and new insights into phage evolution. Genome Res. 13:10421055.
60. Nauts, H. C., and, J. R. McLaren. 1990. Coley toxins–the first century. Adv. Exp. Med. Biol. 267:483500.
61. Nelson, K.,, P. M. Schlievert,, R. K. Selander, and, J. M. Musser. 1991. Characterization and clonal distribution of four alleles of the speA gene encoding pyrogenic exotoxin A (scarlet fever toxin) in Streptococcus pyogenes. J. Exp. Med. 174:12711274.
62. Norrby-Teglund, A.,, G. T. Nepom, and, M. Kotb. 2002. Differential presentation of group A streptococcal superantigens by HLA class II DQ and DR alleles. Eur. J. Immunol. 32:25702577.
63. Oster, H., and, A. Bisno. 2000. Group C and G streptococcal infections: epidemiologic and clinical aspects, p. 184190. In J. J. Fischetti,, R. Novick,, J. J. Ferretti,, D. Portnoy, and, J. Rood(ed.), Gram-Positive Pathogens. ASM Press, Washington, D.C.
64. Petersson, K.,, M. Hakansson,, H. Nilsson,, G. Forsberg,, L. A. Svensson, et al. 2001. Crystal structure of a superantigen bound to MHC class II displays zinc and peptide dependence. EMBO J. 20:33063312.
65. Podbielski, A.,, M. Woischnik,, B. A. Leonard, and, K. H. Schmidt. 1999. Characterization of nra, a global negative regulator gene in group A streptococci. Mol. Microbiol. 31:10511064.
66. Proft, T.,, V. Arcus,, V. Handley,, E. Baker, and, J. Fraser. 2001. Immunological and Biochemical Characterization of Streptococcal Pyrogenic Exotoxins I and J (SPE-I and SPE-J) from Streptococcus pyogenes. J. Immun. 166:67116719.
67. Proft, T.,, S. Moffatt,, K. Weller,, A. Paterson,, D. Martin, and, J. Fraser. 2000. The streptococcal superantigen SMEZ exhibits wide allelic variation, mosaic structure, and significant antigenic variation. J. Exp. Med. 191:17651776.
68. Proft, T.,, S. L. Moffatt,, C. J. Berkahn, and, J. D. Fraser. 1999. Identification and characterization of novel superantigens from Streptococcus pyogenes. J. Exp. Med. 189:89101.
69. Proft, T.,, S. Sriskandan,, L. Yang, and, J. D. Fraser. 2003. Superantigens and streptococcal toxic shock syndrome. Emerg. Infect. Dis. 9: 12111218.
70. Proft, T.,, P. D. Webb,, V. Handley, and, J. D. Fraser. 2003. Two Novel Superantigens Found in Both Group A and Group C Streptococcus. Infect. Immun. 71: 13611369.
71. Reichardt, W.,, H. Müller-Alouf,, J. Alouf, and, W. Köhler. 1992. Erythrogenic toxins A, B, and C: occurrence of the genes and exotoxin formation from clinical Streptococcus pyogenes strains associated with streptococcal toxic shock-like syndrome. FEMS Microbiol. Lett. 79:313322.
72. Rink, L.,, J. Luhm,, M. Koester, and, H. Kirchner. 1996. Induction of a cytokine network by superantigens with parallel TH1 and TH2 stimulation. J. Interferon Cytokine Res. 16:4147.
73. Roussel, A.,, B. F. Anderson,, H. M. Baker,, J. D. Fraser, and, E. N. Baker. 1997. Crystal structure of the streptococcal superantigen SPE-C: dimerization and zinc binding suggest a novel mode of interaction with MHC class II molecules. Nat. Struct. Biol. 4:635643.
74. Sachse, S.,, P. Seidel,, D. Gerlach,, E. Gunther,, J. Rodel,et al. 2002. Superantigen-like gene(s) in human pathogenic Streptococcus dysgalactiae, subsp. equisimilis: genomic localisation of the gene encoding streptococcal pyrogenic exotoxin G (speG(dys)). FEMS Immunol. Med. Microbiol. 34:159167.
75. Schlievert, P.,, A. Assimacopoulos, and, P. Cleary. 1996. Severe invasive group A streptococcal disease: clinical description and mechanisms of pathogenesis. J. Lab. Clin. Med. 127:1322.
76. Schlievert, P. M., and, E. D. Gray. 1989. Group A streptococcal pyrogenic exotoxin (scarlet fever toxin) type A and blastogen A are the same protein. Infect. Immun. 57:18651867.
77. Schlievert, P. M., and, J. A. Kelly. 1982. Staphylococcal pyrogenic exotoxin type C: further characterization. Ann. Intern. Med. 96:982986.
78. Schuh, V.,, V. Hribalova, and, E. Atkins. 1970. The pyrogenic effect of scarlet fever toxin. IV. Pyrogenicity of strain C 203 U filtrate: comparison with some basic characteristics of the known types of scarlet fever toxin. Yale J. Biol. Med. 43:3142.
79. Seal, D. 2001. Necrotizing fasciitis. Curr. Opin. Infect. Dis. 14:127132.
80. Smoot, J. C.,, K. D. Barbian,, J. J. Van Gompel,, L. M. Smoot,, M. S. Chaussee, et al. 2002. Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl. Acad. Sci. USA 99:46684673.
81. Smoot, L. M.,, J. K. McCormick,, J. C. Smoot,, N. P. Hoe,, I. Strickland,et al. 2002. Characterization of two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks. Infect. Immun. 70: 70957104.
82. Sriskandan, S.,, D. Moyes,, L. Buttery,, T. Krausz,, T. Evans,et al. 1996. Streptococcal pyrogenic exotoxin A release, distribution, and role in a murine model of fasciitis and multiorgan failure due to Streptococcus pyogenes. J. Infect. Dis. 173:13991407.
83. Sriskandan, S.,, D. Moyes, and, J. Cohen. 1996. Detection of circulating bacterial superantigen and lympho-toxin-a in patients with streptococcal toxic shock syndrome. Lancet 348:13151316.
84. Sriskandan, S.,, M. Unnikrishnan,, T. Krausz,, H. Dewchand,, S. Van Noorden,et al. 2001. Enhanced susceptibility to superantigen-associated streptococcal sepsis in human leukocyte antigen-DQ transgenic mice. J. Infect. Dis. 184:166173.
85. Stevens, D.,, A. Bryant,, S. Hackett,, A. Chang,, G. Peer,et al. 1996. Group A streptococcal bacteremia: the role of tumor necrosis factor in shock and organ failure. J. Infect. Dis. 173:619626.
86. Stevens, D. L. 1992. Invasive group A streptococcus infections. Clin. Infect. Dis. 14:213.
87. Stevens, D. L. 2000. Streptococcal toxic shock syndrome associated with necrotizing fasciitis. Annu. Rev. Med. 51:271288.
88. Stock, A. H., and, R. J. Lynn. 1969. Extracellular esterases of streptococci and the distribution of specific antibodies in human sera of various age groups. J. Immunol. 102:859869.
89. Sundberg, E. J.,, H. Li,, A. S. Llera,, J. K. McCormick,, J. Tormo,et al. 2002. Structures of two streptococ-cal superantigens bound to TCR β chains reveal diversity in the architecture of T cell signalling complex. Structure 10:687699.
90. Sundberg, E. J.,, Y. Li, and, R. A. Mariuzza. 2002. So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T cell signaling complexes. Curr. Opin. Immunol. 14: 3644.
91. Tiedemann, R. E., and, J. D. Fraser. 1996. Cross-linking of MHC class II molecules by staphylococcal enterotoxin A is essential for antigen-presenting cell and T cell activation. J. Immunol. 157:39583966.
92. Unnikrishnan, M.,, D. Altmann,, T. Proft,, F. Wahid,, J. Cohen,et al. 2002. The bacterial superantigen streptococcal mitogenic exotoxin Z is the major immunoactive agent of Streptococcus pyogenes. J. Immunol. 169:25612569.
93. Virtaneva, K.,, S. Porcella,, M. Graham,, R. Ireland,, C. Johnson,et al. 2005. Longitudinal analysis of the group A Streptococcus transcriptome in experimental pharyngitis in cynomolgus macaques. Proc. Natl. Acad. Sci. USA 102:90149019.
94. Watson, D. 1960. Host-parasite factors in group A streptococcal infections. Pyrogenic and other effects of immunologic distinct exotoxins related to scarlet fever toxins. J. Exp. Med. 111:255284.
95. Weeks, C. R., and, J. J. Ferretti. 1986. Nucleotide sequence of the type A streptococcal exotoxin (erythro-genic toxin) gene from Streptococcus pyogenes bacteriophage T12. Infect. Immun. 52:144150.
96. Welcher, B.,, J. Carra,, L. DaSilva,, J. Hanson,, C. David,et al. 2002. Lethal shock induced by streptococcal pyrogenic exotoxin A in mice transgenic for human leukocyte antigen-DQ8 and human CD4 receptors: implications for development of vaccines and therapeutics. J. Infect. Dis. 186:501510.
97. Willoughby, R., and, R. N. Greenberg. 1983. The toxic shock syndrome and streptococcal pyrogenic exotoxins. Ann. Intern. Med. 98:559.
98. Working Group on Severe Streptococcal Infections. 1993. Defining the group A streptococcal toxic shock syndrome. Rationale and consensus definition. JAMA 269:390391.
99. Yamaoka, J.,, E. Nakamura,, Y. Takeda,, S. Imamura, and, N. Minato. 1998. Mutational analysis of super-antigen activity responsible for the induction of skin erythema by streptococcal pyrogenic exotoxin C. Infect. Immun. 66:50205026.
100. Yang, L.,, M. Thomas,, A. Woodhouse,, D. Martin,, J. Fraser, and, T. Proft. 2005. Involvement of streptococcal mitogenic exotoxin Z in streptococcal toxic shock syndrome. J. Clin. Microbiol. 43:35703573.
101. Yoshioka, T.,, T. Matsutani,, S. Iwagami,, T. Toyosaki-Maeda,, T. Yutsudo,et al. 1999. Polyclonal expansion of TCRBV2- and TCRBV6-bearing T cells in patients with Kawasaki disease. Immunology 96:465472.
102. Yu, C. E., and, J. J. Ferretti. 1989. Molecular epidemiologic analysis of the type A streptococcal exotoxin (erythrogenic toxin) gene (speA) in clinical Streptococcus pyogenes strains. Infect. Immun. 57:37153719.
103. Zabriskie, J. B. 1964. The role of temperate bacteriophage in the production of erythrogenic toxin by group a streptococci. J. Exp. Med. 119:761780.


Generic image for table
Table 1.

Functional properties of streptococcal superantigens

Citation: Fraser J, Proft T. 2007. The Streptococcal Superantigens, p 3-20. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch1

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error