Superantigens: Structure, Function, and Diversity

Matthew D. Baker; K. Ravi Acharya

doi:10.1128/9781555815844.ch8

Chapter 8 : Superantigens: Structure, Function, and Diversity

Authors: Matthew D. Baker¹, K. Ravi Acharya²

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom; 2: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom

Content Type: Monograph

Publication Year: 2007

Category: Bacterial Pathogenesis; Immunology

Book DOI: 10.1128/9781555815844

Chapter DOI: 10.1128/9781555815844.ch8

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

Preview this chapter:

Superantigens: Structure, Function, and Diversity, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815844/9781555814243_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555815844/9781555814243_Chap08-2.gif

Abstract:

Bacterial superantigens (SAgs) are powerful T-cell stimulatory molecules produced primarily by Staphylococcus aureus and Streptococcus pyogenes. Bacterial SAgs possess the unique ability to cross-link major histocompatibility complex (MHC) class II molecules and T-cell receptors, which in turn is responsible for their ability to illicit an immune response several orders of magnitude greater than that of conventional peptide antigens. The division of staphylococcal and streptococcal SAgs into subfamilies based on amino acid sequence, structure, and physiological information has caused some disagreement in the scientific community. Conventional antigens are processed internally by antigen-presenting cells (APCs) and displayed as discrete peptides on the cell surface by MHC class II molecules. These peptide antigens are then recognized by T-cell receptors (TCRs) specific to that peptide. Crystal structures of SAgs in complex with MHC class II molecules via both the generic site (SEB and TSST-1 in complex with HLA-DR1) and the high-affinity site SpeC in complex with HLA-DR2 and SEH in complex with HLA-DR1 have allowed a detailed examination of these interactions. A zinc ion plays a critical role in the binding of SME-Z2, SpeG, and SpeH to MHC class II molecules, as the binding of all three of these toxins to LG-2 cells is significantly reduced by chelating the zinc. The chapter talks about binding to the t-cell receptor, formation of the trimeric complex for signal transduction, and other structural features and idiosyncrasies.

Citation: Baker M, Acharya K. 2007. Superantigens: Structure, Function, and Diversity, p 121-135. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch8

Key Concept Ranking

MHC Class II: 0.6326829
MHC Class I: 0.47830844
Severe Acute Respiratory Syndrome: 0.44924498

0.6326829

Highlighted Text: Show | Hide

Full text loading...

References

/content/book/10.1128/9781555815844.ch08

1. Abe, J.,, T. Takeda,, Y. Watanabe,, H. Nakao,, N. Kobayashi,, D. Y. Leung, and, T. Kohsaka. 1993. Evidence for superantigen production by Yersinia pseudotuberculosis. J. Immunol. 151: 4183– 4188.

2. Abrahmsen, L.,, M. Dohlsten,, S. Segren,, P. Bjork,, E. Jonsson, and, T. Kalland. 1995. Characterization of two distinct MHC class II binding sites in the superantigen Staphylococcal enterotoxin A. EMBO J. 14: 2978– 2986.

3. Acharya, K. R.,, E. F. Passalacqua,, E. Y. Jones,, K. Harlos,, D. I. Stuart,, R. D. Brehm, and, H. S. Tranter. 1994. Structural basis of superantigen action inferred from crystal structure of toxic-shock syndrome toxin-1. Nature 367: 94– 97.

4. Alber, G.,, D. K. Hammer, and, B. Fleischer. 1 990. Relationship between enterotoxic- and T lymphocyte-stimulating activity of Staphylococcal enterotoxin B. J. Immunol. 144: 4501– 4506.

5. Al-Shangiti, A. M.,, C. E. Naylor,, S. P. Nair,, D. C. Briggs,, B. Henderson, and, B. M. Chain. 2004. Structural relationships and cellular tropism of Staphylococcal superantigen-like proteins. Infect. Immun. 72: 4261– 4270.

6. Anderson, P. S.,, P. M. Lavoie,, R. P. Sekaly,, H. Churchill, and, D. M. Kranz. 1999. Role of the T cell receptor α-chain in stabilising TCR-Superantigen-MHC class II complexes. Immunity 10: 473– 483.

7. Arad, G.,, R. Levy,, D. Hillman, and, R. Kaempfer. 2000. Superantigen antagonist protects against lethal shock and defines a new domain for T-cell activation. Nat. Med. 6: 414– 421.

8. Arcus, V. L.,, R. Langley,, T. Proft,, J. D. Fraser, and, E. N. Baker. 2002. The three-dimensional structure of a superantigen-like protein, SET3, from a pathogenicity island of the Staphylococcus aureus genome. J. Biol. Chem. 277: 32274– 32281.

9. Baker, M. D., and, K. R. Acharya. 2003 Superantigens. Structure, function, and diversity. Methods. Mol. Biol. 214: 1– 31.

10. Baker, M. D., and, K. R. Acharya. 2004. Superantigens: structure-function relationships. Int. J. Med. Microbiol. 293: 529– 537.

11. Baker, M. D.,, I. Gendlina,, C. M. Collins, and, K. R. Acharya. 2004. Crystal structure of a dimeric form of Streptococcal pyrogenic exotoxin A (SpeA1). Protein. Sci. 13: 2285– 2290.

12. Bernatchez, C.,, R. Al-Daccak,, P. E. Mayer,, K. Mehindate,, L. Rink,, S. Mecheri, and, W. Mourad. 1997. Functional analysis of Mycoplasma arthritidis-derived mitogen interactions with class II molecules. Infect. Immun. 65: 2000– 2005.

13. Cole, B. C. 1991. The immunobiology of Mycoplasma arthritidis and its superantigen MAM. Curr. Top. Microbiol. Immunol. 174: 107– 119.

14. Cole, B. C.,, K. L. Knudtson,, A. Oliphant,, A. D. Sawitzke,, A. Pole,, M. Manohar,, L. S. Benson,, E. Ahmed, and, C. L. Atkin. 1996. The sequence of the Mycoplasma arthritidis superantigen, MAM: identification of functional domains and comparison with microbial superantigens and plant lectin mitogens. J. Exp. Med. 183: 1105– 1110.

15. Cuff, L.,, R. G. Ulrich, and, M. A. Olson. 2003. Prediction of the multimeric assembly of Staphylococcal enterotoxin A with cell-surface protein receptors. J. Mol. Graph. Model. 21: 473– 486.

16. Davis, S. J.,, S. Ikemizu,, E. J. Evans,, L. Fugger,, T. R. Bakker, and, P. A. van der Merwe. 2003. The nature of molecular recognition by T cells. Nat. Immunol. 4: 217– 224.

17. Deresiewicz, R. L.,, J. Woo,, M. Chan,, R. W. Finberg, and, D. L. Kasper. 1994. Mutations affecting the activity of toxic shock syndrome toxin-1. Biochemistry 33: 12844– 12851.

18. Deringer, J. R.,, R. J. Ely,, C. V. Stauffacher, and, G. A. Bohach. 1996. Subtype-specific interactions of type C Staphylococcal enterotoxins with the T-cell receptor. Mol. Microbiol. 22: 523– 534.

19. Donadini, R.,, C. W. Liew,, A. H. Kwan,, J. P. Mackay, and, B. A. Fields. 2004. Crystal and solution structures of a superantigen from Yersinia pseudotuberculosis reveal a jelly-roll fold. Structure 12: 145– 156.

20. Etongue-Mayer, P.,, M. A. Langlois,, M. Ouellette,, H. Li,, S. Younes,, R. Al-Daccak, and, W. Mourad. 2002. Involvement of zinc in the binding of Mycoplasma arthritidis-derived mitogen to the proximity of the HLA-DR binding groove regardless of histidine 81 of the β chain. Eur. J. Immunol. 32: 50– 58.

21. Ferretti, J. J.,, W. M. McShan,, D. Ajdic,, D. J. Savic,, G. Savic,, K. Lyon,, C. Primeaux,, S. Sezate,, A. N. Suvorov,, S. Kenton,, H. S. Lai,, S. P. Lin,, Y. Qian,, H. G. Jia,, F. Z. Najar,, Q. Ren,, H. Zhu,, L. Song,, J. White,, X. Yuan,, S. W. Clifton,, B. A. Roe, and, R. McLaughlin. 2001. Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc. Natl. Acad. Sci. USA 98: 4658– 4663.

22. Fields, B. A.,, E. L. Malchiodi,, H. Li,, X. Ysern,, C. V. Stauffacher,, P. M. Schlievert,, K. Karjalainen, and, R. A. Mariuzza. 1996. Crystal structure of a T-cell receptor β-chain complexed with a superantigen. Nature 384: 188– 192.

23. Fraser, J. D.,, R. G. Urban,, J. L. Strominger, and, H. Robinson. 1992. Zinc regulates the function of two superantigens. Proc. Natl. Acad. Sci USA 89: 5507– 5511.

24. Germain, R. N. 1997. T-cell signalling: the importance of receptor clustering. Curr. Biol. 7: 640– 644.

25. Haas, P. J.,, C. J.C. de Haas,, M. J. J. C. Poppelier,, K.P. M. van Kessel,, J. A.G. van Strijp,, K. Dijkstra,, R. M. Scheek,, H.W. Fan,, J. A. Kruijtzer,, R. M.J. Liskamp, and, J. Kemmink. 2005. The Structure of C5a receptor-blocking domain of chemotaxis inhibitory protein of Staphylococcus aureus is related to a group of immune evasive molecules. J. Mol. Biol. 353: 859– 872.

26. Hakansson, M.,, K. Petersson,, H. Nilsson,, G. Forsberg,, P. Bjork,, P. Antonsson, and, L. A. Svensson. 2000. The crystal structure of Staphylococcal enterotoxin H: implications for binding properties to MHC class II and TcR molecules. J. Mol. Biol. 302: 527– 537.

27. Harris, T. O., and, M. J. Betley. 1995. Biological activities of Staphylococcal enterotoxin type A mutants with N-terminal substitutions. Infect. Immun. 63: 2133– 2140.

28. Hoffman, M.,, M. Tremaine,, J. Mansfield, and, M. Betley. 1996. Biochemical and mutational analysis of the histidine residues of Staphylococcal enterotoxin A. Infect. Immun. 64: 885– 890.

29. Hovde, C. J.,, J. C. Marr,, M. L. Hoffmann,, S. P. Hackett,, Y. I. Chi,, K. K. Crum,, D. L. Stevens,, C. V. Stauffacher, and, G. A. Bohach. 1994. Investigation of the role of the disulphide bond in the activity and structure of Staphylococcal enterotoxin C1. Mol. Microbiol. 13: 897– 909.

30. Hudson, K. R.,, H. Robinson, and, J. D. Fraser. 1993. Two adjacent residues in Staphylococcal enterotoxins A and E determine T cell receptor Vβ specificity. J. Exp. Med. 177: 175– 184.

31. Ito, Y.,, G. Seprenyi,, J. Abe, and, T. Kohsaka. 1999. Analysis of functional regions of YPM, a superantigen derived from gram-negative bacteria. Eur. J. Biochem. 263: 326– 337.

32. Jardetzky, T. S.,, J. H. Brown,, J. C. Gorga,, L. J. Stern,, R. G. Urban,, Y. I. Chi,, C. Stauffacher,, J. L. Strominger, and, D. C. Wiley. 1994. Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen. Nature 368: 711– 718.

33. Kappler, J.,, B. Kotzin,, L. Herron,, E. W. Gelfand,, R. D. Bigler,, A. Boylston,, S. Carrel,, D. N. Posnett,, Y. Choi, and, P. Marrack. 1989. Vβ specific stimulation of human T cells by Staphylococcal toxins. Science 244: 811– 813.

34. Kappler, J. W.,, A. Herman,, J. Clements, and, P. Marrack. 1992. Mutations defining functional regions of the superantigen staphylococcal enterotoxin B. J. Exp. Med. 175: 387– 396.

35. Kim, J.,, R. G. Urban,, J. L. Strominger, and, D. C. Wiley. 1994. Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1. Science 266: 1870– 1874.

36. Kline, J. B., and, C. M. Collins. 1997. Analysis of the interaction between the bacterial superantigen Streptococcal pyrogenic exotoxin A (SpeA) and the human T-cell receptor. Mol. Microbiol. 24: 191– 202.

37. Kuroda, M.,, T. Ohta,, I. Uchiyama,, T. Baba,, H. Yuzawa,, I. Kobayashi,, L. Cui,, A. Oguchi,, K. Aoki,, Y. Nagai,, J. Lian,, T. Ito,, M. Kanamori,, H. Matsumaru,, A. Maruyama,, H. Murakami,, A. Hosoyama,, Y. Mizutani-Ui,, N. K. Takahashi,, T. Sawano,, R. Inoue,, C. Kaito,, K. Sekimizu,, H. Hirakawa,, S. Kuhara,, S. Goto,, J. Yabuzaki,, M. Kanehisa,, A. Yamashita,, K. Oshima,, K. Furuya,, C. Yoshino,, T. Shiba,, M. Hattori,, N. Ogasawara,, H. Hayashi, and, K. Hiramatsu. 2001. Whole genome sequencing of methicillin-resistant Staphylococcus aureus. Lancet 357: 1225– 1240.

38. Langlois, M. A.,, Y. El Fakhry, and, W. Mourad. 2003. Zinc-binding sites in the N terminus of Mycoplasma arthritidis-derived mitogen permit the dimer formation required for high affinity binding to HLA-DR and for T cell activation. J. Biol. Chem. 278: 22309– 22315.

39. Lavoie, P. M.,, H. McGrath,, N. H. Shoukry,, P. A. Cazenave,, R. P. Sekaly, and, J. Thibodeau. 2001. Quantitative relationship between MHC class II-superantigen complexes and the balance of T cell activation versus death. J. Immunol 166: 7229– 7237.

40. Leder, L.,, A. Llera,, P. M. Lavoie,, M. I. Lebedeva,, H. Li,, R. P. Sekaly,, G. A. Bohach,, P. J. Gahr,, P. M. Schlievert,, K. Karjalainen, and, R. A. Mariuzza. 1998. A mutational analysis of the binding of Staphylococcal enterotoxins B and C3 to the T cell receptor β-chain and major histocompatibility complex class II. J. Exp. Med. 187: 823– 833.

41. Li, H.,, A. Llera, and, R. A. Mariuzza. 1998. Structure-function studies of T-cell receptor-superantigen interactions. Immunol. Rev. 163: 177– 186.

42. Li, H.,, A. Llera,, D. Tsuchiya,, L. Leder,, X. Ysern,, P. M. Schlievert,, K. Karjalainen, and, R. A. Mariuzza. 1998. Three-dimensional structure of the complex between a T cell receptor β-chain and the superantigen Staphylococcal enterotoxin B. Immunity 9: 807– 816.

43. Li, Y.,, H. Li,, N. Dimasi,, J. K. McCormick,, R. Martin,, P. Schuck,, P. M. Schlievert, and, R. A. Mariuzza. 2001. Crystal structure of a superantigen bound to the high-affinity, zinc- dependent site on MHC class II. Immunity 14: 93– 104.

44. Li, Y.,, C. Luo,, W. Lei,, Z. Xu,, C. Zeng,, S. Bi,, J. Yu,, J. Wu, and, H. Yang. 2004. Structure-based preliminary analysis of immunity and virulence of SARS Coronavirus. Viral. Immun. 17: 528– 534.

45. Marrack, P., and, J. Kappler. 1990. The staphylococcal enterotoxins and their relatives. Science 248: 1066.

46. Omoe, K.,, D. L. Hu,, H. Takahashi-Omoe,, A. Nakane, and, K. Shinagawa. 2003. Identification and characterization of a new Staphylococcal enterotoxin-related putative toxin encoded by two kinds of plasmids. Infect. Immun. 71: 6088– 6094.

47. Orwin, P. M.,, D. Y. Leung,, T. J. Tripp,, G. A. Bohach,, C. A. Earhart,, D. H. Ohlendorf, and, P. M. Schlievert. 2002. Characterization of a novel Staphylococcal enterotoxin-like superantigen, a member of the group V subfamily of pyrogenic toxins. Biochemistry 41: 14033– 14040.

48. Papageorgiou, A. C.,, M. D. Baker,, J. D. McLeod,, S. K. Goda,, C. N. Manzotti,, D. M. Sansom,, H. S. Tranter, and, K. R. Acharya. 2004. Identification of a secondary zinc-binding site in Staphylococcal enterotoxin C2. Implications for superantigen recognition. J. Biol. Chem. 279: 1297– 1303.

49. Papageorgiou, A. C.,, C. M. Collins,, D. M. Gutman,, J. B. Kline,, S. M. O’Brien,, H. S. Tranter, and, K. R. Acharya. 1999. Structural basis for the recognition of superantigen streptococcal pyrogenic exotoxin A (SpeA1) by MHC class II molecules and T-cell receptors. EMBO J. 18: 9– 21.

50. Petersson, K.,, M. Hakansson,, H. Nilsson,, G. Forsberg,, L. A. Svensson,, A. Liljas, and, B. Walse. 2001. Crystal structure of a superantigen bound to MHC class II displays zinc and peptide dependence. EMBO J. 20: 3306– 3312.

51. Petersson, K.,, H. Pettersson,, N. J. Skartved,, B. Walse, and, G. Forsberg. 2003. Staphylococcal enterotoxin H induces V α specific expansion of T cells. J. Immunol. 170: 4148– 4154.

52. Pless, D. D.,, G. Ruthel,, E. K. Reinke,, R. G. Ulrich, and, S. Bavari. 2005. Persistence of zinc-binding bacterial superantigens at the cell surface of antigen-presenting cells contributes to the extreme potency of these superantigens as T-cell activators. Infect. Immun. 73: 5358– 5366.

53. 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: 89– 102.

54. 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: 635– 643.

55. Schlievert, P. M.,, L. M. Jablonski,, M. Roggiani,, I. Sadler,, S. Callantine,, D. T. Mitchell,, D. H. Ohlendorf, and, G. A. Bohach. 2000. Pyrogenic toxin superantigen site specificity in toxic shock syndrome and food poisoning in animals. Infect. Immun. 68: 3630– 3634.

56. Spero, L., and, B. A. Morlock. 1978. Biological activities of the peptides of Staphylococcal enterotoxin C formed by limited tryptic hydrolysis. J. Biol. Chem. 253: 8787– 8791.

57. Stevens, K. R.,, M. Van,, J. G. Lamphear, and, R. R. Rich. 1996. Altered orientation of Streptococcal super-antigen (SSA) on HLA-DR1 allows unconventional regions to contribute to SSA Vβ specificity. J. Immunol. 157: 4970– 4978.

58. Sundberg, E., and, T. S. Jardetzky. 1999. Structural basis for HLA-DQ binding by the Streptococcal super-antigen SSA. Nat. Struct. Biol. 6: 123– 129.

59. Sundberg, E. J.,, H. Li,, A. S. Llera,, J. K. McCormick,, J. Tormo,, P. M. Schlievert,, K. Karjalainen, and, R. A. Mariuzza. 2002. Structures of two Streptococcal superantigens bound to TCR β chains reveal diversity in the architecture of T cell signalling complexes. Structure 10: 687– 699.

60. Sundstrom, M.,, L. Abrahmsen,, P. Antonsson,, K. Mehindate,, W. Mourad, and, M. Dohlsten. 1996. The crystal structure of Staphylococcal enterotoxin type D reveals Zn +-mediated homodimerization. EMBO J. 15: 6832– 6840.

61. Swaminathan, S.,, W. Furey,, J. Pletcher, and, M. Sax. 1992. Crystal structure of Staphylococcal enterotoxin B, a superantigen. Nature 359: 801– 806.

62. Swaminathan, S.,, W. Furey,, J. Pletcher, and, M. Sax. 1995. Residues defining V β specificity in staphylococcal enterotoxins. Nature. Struct. Biol. 2: 680– 686.

63. Thomas, P.,, P. D. Webb,, V. Handley, and, J. D. Fraser. 2004. Identification & characterisation of the two novel Streptococcal pyrogenic exotoxins SPE-L & SPE-M. Indian J. Med. Res. 119(Suppl.): 37– 43.

64. Tiedemann, R. E.,, R. J. Urban,, J. L. Strominger, and, J. D. Fraser. 1995. Isolation of HLA-DR1.(Staphylococcal enterotoxin A)2 trimers in solution. Proc. Natl. Acad. Sci. USA 92: 12156– 12159.

65. Uchiyama, T.,, T. Miyoshi-Akiyama,, H. Kato,, W. Fujimaki,, K. Imanishi, and, X. J. Yan. 1993. Superantigenic properties of a novel mitogenic substance produced by Yersinia pseudotuberculosis isolated from patients manifesting acute and systemic symptoms. J. Immunol. 151: 4407– 4413.

66. Wen, R.,, D. R. Broussard,, S. Surman,, T. L. Hogg,, M. A. Blackman, and, D. L. Woodland. 1997. Carboxy-terminal residues of major histocompatibility complex class II- associated peptides control the presentation of the bacterial superantigen toxic shock syndrome toxin-1 to T cells. Eur. J. Immunol. 27: 772– 781.

67. Williams, R. J.,, J. M. Ward,, B. Henderson,, S. Poole,, B. P. O’Hara,, M. Wilson, and, S. P. Nair. 2000. Identification of a novel gene cluster encoding Staphylococcal exotoxin-like proteins: characterization of the prototypic gene and its protein product, SET1. Infect. Immun. 68: 4407– 4415.

68. Woodland, D. L.,, R. Wen, and, M. A. Blackman. 1997. Why do superantigens care about peptides? Immunol. Today 18: 18– 22.

69. Zhao, Y.,, Z. Li,, S. J. Drozd,, Y. Guo,, W. Mourad, and, H. Li. 2004. Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex. Structure 12: 277– 288.

Tables

Superantigens: Structure, Function, and Diversity

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815844.ch08-1,webId=/content/author/10.1128/9781555815844.ch08-1,properties={foaf_givenname=Matthew D., foaf_name=Matthew D. Baker, foaf_surname=Baker, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815844.ch08-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815844.ch08-2,webId=/content/author/10.1128/9781555815844.ch08-2,properties={foaf_givenname=K. Ravi, foaf_name=K. Ravi Acharya, foaf_surname=Acharya, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815844.ch08-aff2]]}]]

/content/10.1128/9781555815844.ch08.ch08tab01

Table 1.

Role of zinc ion in superantigen function

Table 1.

Role of zinc ion in superantigen function