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Journal of Clinical Immunology

, Volume 12, Issue 3, pp 149–162 | Cite as

Superantigens: Biology, immunology, and potential role in disease

  • Charles G. Drake
  • Brian L. Kotzin
Special Article

Abstract

Superantigens are unique products of bacteria and viruses which, in combination with class II major histocompatibility complex molecules, are capable of stimulating a large fraction of T cells in an affected individual. This stimulation primarily involves the variable region of the T cell receptor beta chain (Vβ). The discovery of superantigens and the elucidation of their immunologic properties have provided valuable tools for the investigation of the immune system in both normal and diseased animals. Most importantly, recent work suggests that superantigens play a role in a number of diverse pathological conditions, including toxic shock syndrome and autoimmune diseases such as rheumatoid arthritis.

Key words

Superantigens T-cell receptor T-cell activation bacterial toxins endogenous retroviruses toxic shock syndrome autoimmune disease 

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References

  1. 1.
    White H, Herman A, Pullen AM, Kubo R, Kappler JW, Marrack P: The Vβ specific superantigen staphylococcal enterotoxin B: Stimulation of mature T cells and clonal deletion in neonatal mice. Cell 56:27–35, 1989Google Scholar
  2. 2.
    Zinkernagel R, Doherty P: H-2-compatibility requirement for T cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus: Different cytotoxic T cell specificities are associated with structures from H-2k or H-2d. J Exp Med 141:1427–1436, 1975Google Scholar
  3. 3.
    Festenstein H: Immunogenetic and biological aspects of in vitro lymphocyte allotransformation (MLR) in the mouse. Transplant Rev 15:62–88, 1973Google Scholar
  4. 4.
    Palmer E: Infectious origins of superantigens. Curr Bio 1:74–76, 1991Google Scholar
  5. 5.
    Pullen AM, Marrack P, Kappler JW: The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature 335:796–801, 1988Google Scholar
  6. 6.
    Marrack P, Kappler J: The staphylococcal enterotoxins and their relatives. Science 248:705–711, 1990Google Scholar
  7. 7.
    Kappler JW, Wade T, White J, Kushnir E, Blackman M, Bill J, Roehm N, Marrack P: A T cell receptor Vβ segment that imparts reactivity to a class II major histocompatibility complex product. Cell 49:263–271, 1987Google Scholar
  8. 8.
    Kappler JW, Roehm N, Marrack P: T cell tolerance by clonal elimination in the thymus. Cell 49:273–280, 1987Google Scholar
  9. 9.
    Herman A, Kappler JW, Marrack P, Pullen AM: Superantigens: Mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol 9:745–772, 1991Google Scholar
  10. 10.
    Kappler JW, Staerz U, White J, Marrack PC: Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature 332:35–40, 1988Google Scholar
  11. 11.
    MacDonald HR, Schneider R, Lees RK, Howe RC, Acha-Orbea H, Festenstein H, Zinkernagel RM, Hengartner H: T-cell receptor Vβ use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature 332:40–45, 1988Google Scholar
  12. 12.
    Woodland DL, Happ MP, Bill J, Palmer E: Requirement for cotolerogenic gene products in the clonal deletion of I-E reactive T cells. Science 247:964–967, 1990Google Scholar
  13. 13.
    Abe R, Vacchio MS, Fox B, Hodes RJ: Preferential expression of the T-cell receptor Vβ3 gene by Mlsc reactive T cells. Nature 335:827–830, 1988Google Scholar
  14. 14.
    Vacchio MS, Ryan JJ, Hodes RJ: Characterization of the ligand(s) responsible for negative selection of Vβ11- and Vβ12-expressing T cells: effects of a new Mls determinant. J Exp Med 172:807–813, 1990Google Scholar
  15. 15.
    Woodland DL, Happ MP, Gollob KJ, Palmer E: An endogenous retrovirus mediating deletion of αβ T cells? Nature 349:529–530, 1991Google Scholar
  16. 16.
    Frankel WN, Rudy C, Coffin JM, Huber BT: Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice. Nature 349:526–528, 1991Google Scholar
  17. 17.
    Dyson PJ, Knight AM, Fairchild S, Simpson E, Tomonari K: Genes encoding ligands for deletion of Vβ11 T cells cosegregate with mammary tumour virus genomes. Nature 349:531–532, 1991Google Scholar
  18. 18.
    Marrack P, Kushnir E, Kappler J: A maternally inherited superantigen encoded by a mammary tumour virus. Nature 349:524–526, 1991Google Scholar
  19. 19.
    Choi Y, Kappler JW, Marrack P: A superantigen encoded in the open reading frame of the 3′ long terminal repeat of mouse mammary tumor virus. Nature 350:203–207, 1991Google Scholar
  20. 20.
    Pullen AM, Potts W, Wakeland EK, Kappler J, Marrack P: Surprisingly uneven distribution of the T cell receptor Vβ repertoire in wild mice. J Exp Med 171:49–62, 1990Google Scholar
  21. 21.
    Bohach GA, Fast DJ, Nelson RD, Schilevert PM: Staphylococcal and streptococcal pyrogenic toxins involved in toxic shock syndrome and related illnesses. Crit Rev Microbio 117:251–272, 1990Google Scholar
  22. 22.
    Abe J, Forrester J, Nakahara T, Lafferty JA, Kotzin BL, Leung DYM: Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B. J Immunol 146:3747–3750, 1991Google Scholar
  23. 23.
    Misfeldt ML: Microbial “superantigens.” Infect Immun 58:2409–2413, 1990Google Scholar
  24. 24.
    Friedman SM, Crow MK, Tumang JR, Tumang M, Xu Y, Hodtsev AS, Cole BC, Postnett DN: Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against Vβ17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells. J Exp Med 174:891–900, 1991Google Scholar
  25. 25.
    Hügin AW, Vacchio MS, Morse HC: A virus-encoded “superantigen” in a retrovirus-induced immunodeficiency syndrome of mice. Science 252:424–426, 1991Google Scholar
  26. 26.
    Imberti L, Sottini A, Bettinardi A, Puoti M, Primi D: Selective depletion in HIV infection of T cells that bear specific Vβ sequences. Science 254:860–862, 1991Google Scholar
  27. 27.
    Webb SR, Molnar-Kimber K, Bruce J, Sprent J, Wilson DB: T cell clones with dual specificity for Mls and various major histocompatibility complex determinants. J Exp Med 154:1970–1974, 1981Google Scholar
  28. 28.
    Janeway CA, Yagi J, Conrad PJ, Katz ME, Jones B, Vroegop S, Bixser S: T-cell responses to Mls and to bacterial proteins that mimic its behavior. Immunol Rev 107:61–88, 1989Google Scholar
  29. 29.
    Buxser S, Bonventre PF, Archer DL: Specific receptor binding of staphylococcal enterotoxins by murine splenic lymphocytes. Infect Immun 33:827–833, 1981Google Scholar
  30. 30.
    Fischer H, Dohlsten M, Lindvall M, Sjögren H, Carlsson R: Binding of staphylococcal enterotoxin A to HLA-DR on B cell lines. J Immunol 142:3151–3157, 1989Google Scholar
  31. 31.
    Mollick JA, Cook RG, Rich RR: Class II MHC molecules are specific receptors for staphylococcus enterotoxin A. Science 244:817–820, 1989Google Scholar
  32. 32.
    Scholl PR, Diez A, Geha RS: Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 bind to distinct sites on HLA-DR and HLA-DQ molecules. J Immunol 143:2583–2588, 1989Google Scholar
  33. 33.
    Herman A, Croteau G, Sekaly R, Kappler J, Marrack P: HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells. J Exp Med 172:709–717, 1990Google Scholar
  34. 34.
    Yagi J, Baron J, Buxser S, Janeway CA Jr: Bacterial proteins that mediate the association of a defined subset of T cell receptor: CD4 complexes with class II MHC. J Immunol 144:892–901, 1990Google Scholar
  35. 35.
    Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC: Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329:506–512, 1987Google Scholar
  36. 36.
    Brown JH, Jardetsky T, Saper MA, Samraoui B, Bjorkman PJ, Wiley DC: A hypothetical model of the foreign antigen binding site of class II histocompatibility models. Nature 332:845–850, 1988Google Scholar
  37. 37.
    Dellabona P, Peccoud J, Kappler J, Marrack P, Benoist C, Mathis D: Superantigens interact with MHC class II molecules outside of the antigen groove. Cell 62:1115–1121, 1990Google Scholar
  38. 38.
    Fleischer B, Schrezenmeier H: T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J Exp Med 167:1697–1707, 1988Google Scholar
  39. 39.
    Bauer A, Rutenfranz I, Kirchner H: Processing requirements for T cell activation by Mycoplasma arthritidis derived mitogen. Eur J Immunol 18:2109–2112, 1988Google Scholar
  40. 40.
    Davis MM, Bjorkman PJ: T-cell antigen receptor genes and T-cell recognition. Nature 334:398–402, 1988Google Scholar
  41. 41.
    Clothia C, Boswell DR, Lesk AM: The outline structure of the T-cell αβ receptor. EMBO J 7:3745–3755, 1988Google Scholar
  42. 42.
    Choi Y, Herman A, DiGiusto D, Wade T, Marrack P, Kappler J: Residues of the variable region of the T-cell receptor β-chain that interact with S. aureus toxin superantigens. Nature 346:471–473, 1990Google Scholar
  43. 43.
    Cazenave P, Marche PN, Jouvin-Marche E, Voegtlé D, Bonhomme F, Bandeira A, Coutinho A: Vβ17 gene polymorphism in wild-derived mouse strains: Two amino acid substitutions in the Vβ17 region greatly alter T cell receptor specificity. Cell 63:717–728, 1990Google Scholar
  44. 44.
    Pullen AM, Wade TW, Marrack P, Kappler JW: Identification of the region of the T cell receptor β chain that interacts with the self-superantigen Mls-1a. Cell 61:1365–1374, 1990Google Scholar
  45. 45.
    Webb S, Morris C, Sprent J: Extrathymic tolerance of mature T cells: Clonal elimination as a consequence of immunity. Cell 63:1249–1256, 1990Google Scholar
  46. 46.
    Kawabe Y, Ochi A: Programmed cell death and extrathymic reduction of Vβ8+CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature 349:245–248, 1991Google Scholar
  47. 47.
    Schwartz RH: Acquisition of immunologic self-tolerance. Cell 57:1073–1081, 1989Google Scholar
  48. 48.
    Kotzin BL, Kappler JW, Marrack PC, Herron LR: T cell tolerance to self antigens in New Zealand hybrid mice with lupus-like disease. J Immunol 143:89–94, 1989Google Scholar
  49. 49.
    Kotzin BL, Babcock SK, Herron LR: Delection of potentially self-reactive T cell receptor specificities in L3T4, Lyt-2 T cells of lpr mice. J Exp Med 168:2221–2229, 1988Google Scholar
  50. 50.
    Todd JK: Toxic shock syndrome. Clin Microbiol Rev 1:432–446, 1988Google Scholar
  51. 51.
    Choi Y, Kotzin BL, Herron L, Callahan J, Marrack P, Kappler J: Interaction of S. aureus toxin superantigens with human T cells. Proc Natl Acad Sci USA 86:8941–8945, 1989Google Scholar
  52. 52.
    Choi Y, Lafferty JA, Clements JR, Todd JK, Gelfand EW, Kappler J, Marrack P, Kotzin BL: Selective expansion of T cells expressing Vβ2 in toxic shock syndrome. J Exp Med 172:981–984, 1990Google Scholar
  53. 53.
    Parsonnet J: Mediators in the pathogenesis of toxic shock syndrome: Overview. Rev Infect Dis II (Suppl 1):s263-s269, 1989Google Scholar
  54. 54.
    Marrack P, Blackman M, Kushnir E, Kappler J: The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells. J Exp Med 171:455–464, 1990Google Scholar
  55. 55.
    Kawasaki T: Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children: clinical observations of 50 cases. Jpn J Allergol 16:178–222, 1967Google Scholar
  56. 56.
    Rauch A, Hurwitz E: Centers for Disease Control case definition for Kawasaki syndrome. Pediatr Infect Dis 4:702–703, 1985Google Scholar
  57. 57.
    Leung DYM: Immunologic aspects of Kawasaki disease. J Rheumatol 17 (Suppl 24):15–18, 1990Google Scholar
  58. 58.
    Abe J, Kotzin BL, Jujo K, Melish ME, Glode MP, Kohsaka T, Leung DYM: Selective expansion of T cells expressing Vβ2 and Vβ8 in Kawasaki disease. Proc Natl Acad Sci USA, in press, 1992Google Scholar
  59. 59.
    Gregersen PK, Silver J, Winchester RJ: The shared epitope hypothesis: An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arth Rheum 30:1205–1213, 1987Google Scholar
  60. 60.
    Paliard X, West SG, Lafferty JA, Clements JR, Kappler JW, Marrack P, Kotzin BL: Evidence for the effects of a superantigen in rheumatoid arthritis. Science 253:325–329, 1991Google Scholar
  61. 61.
    Stevens DL, Tanner MH, Winship J, Swarts R, Ries KM, Schlievert PM, Kaplan E: Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A. N Engl J Med 321:1–7, 1989Google Scholar
  62. 62.
    Dale JB, Beachey EH: Multiple, heart cross-reactive epitopes of streptococcal M proteins. J Exp Med 161:113–122, 1985Google Scholar
  63. 63.
    Tomai M, Kotb M, Majumdar G, Beachey EH: Superantigenicity of streptococcal M protein. J Exp Med 172:359–362, 1990Google Scholar
  64. 64.
    Portanova JP, Kotzin BL: Lupus-like autoimmunity in murine graft-versus-host disease. Concepts Immunopathol 6:119–140, 1988Google Scholar
  65. 65.
    Friedman SM, Posnett DN, Tumang JR, Crow MK: A potential role for microbial superantigens in the pathogenesis of systemic autoimmune disease. Arth Rheum 34:468–480, 1991Google Scholar
  66. 66.
    Tumang JR, Posnett DN, Cole BC, Crow MK, Friedman SM: Helper T-cell differentiation mediated by a mycoplasmal superantigen bridge. J Exp Med 171:2153–2158, 1990Google Scholar
  67. 67.
    Okada CY, Weissman IL: Relative Vβ transcript levels in thymus and peripheral lymphoid tissues from various mouse strains. Inverse correlation of I-E and Mls expression with relative abundance of several Vβ transcripts in peripheral lymphoid tissues. J Exp Med 169:1703–1719, 1989Google Scholar
  68. 68.
    Happ MP, Woodland DL, Palmer E: A third T cell receptor Vβ gene encodes reactivity to Mls-1a gene products. Proc Natl Acad Sci USA 86:6293–6296, 1989Google Scholar
  69. 69.
    Kappler J, Kotzin B, Herron L, Gelfand EW, Bigler RD, Boylston A, Carrel S, Posnett DN, Choi Y, Marrack P: Vβ-specific stimulation of human T cells by staphylococcal toxins. Science 244:811–813, 1989Google Scholar
  70. 70.
    Callahan JE, Herman J, Kappler JW, Marrack P: Stimulation of B10.BR T cells with superantigenic staphylococcal toxins. J Immunol 144:2473–2479, 1990Google Scholar
  71. 71.
    Cole BC, Kartchner DR, Wells DJ: Stimulation of mouse lymphocytes by a mitogen derived from mycoplasma arthritidis (MAM) VIII. Selective activation of T cells expressing distinct Vβ T cell receptors from various strains of mice by the “superantigen” MAM. J Immunol 144:425–431, 1990Google Scholar
  72. 72.
    Janeway CA Jr: Self superantigens? Cell 63:659–661, 1990Google Scholar
  73. 73.
    Kotzin BL, Herron LR, Babcock SK, Portanova JP, Palmer E: Self-reactive T cells in murine lupus: Analysis of genetic contributions and development of self-tolerance. Clin Immunol Immunopathol 53:S35-S46, 1989Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Charles G. Drake
    • 1
    • 2
  • Brian L. Kotzin
    • 1
    • 2
  1. 1.Departments of Pediatrics and MedicineNational Jewish Center for Immunology and Respiratory MedicineDenver
  2. 2.Departments of Medicine and Microbiology/ImmunologyUniversity of Colorado Health Sciences CenterDenver

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