Chapter 4 : Viral Superantigens in Mice and Humans

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Adaptive immunity relies on the antigen-specific B cell (BCR) and T cell (TCR) receptors to survey for pathogenic events. Upon recognition of a microbe by these receptors, an immune response is initiated, resulting in the differentiation of the antigen-specific lymphocytes into effector cells, which eliminate the pathogen. According to the IMGT database, there are 23 and 18 functional T cell (TCR) receptors Vβ-families in humans and mice, respectively. The majority of known superantigens (SAgs) are of either bacterial or viral origin, the prototypes being the bacterial pathogens and and the murine mammary tumor virus (MMTV). While the exogenous virus encoded SAg is critical for the viral infection, the expression of endogenous MMTV SAgs leads to thymic deletion of T cells with the corresponding Vβ-chains, hence rendering the mice resistant to infection by exogenous MMTV encoding SAgs with the same Vβ specificity. During thymic maturation, only T cells that receive signals above a certain threshold survive by undergoing positive selection. Expression of a strong endogenous SAg during the negative selection process often results in thymic deletion of the entire population of T-cell expression TCR Vβ-chains that are reactive to the SAg, while a weak SAg activity leads to partial deletion or anergy of the reactive T cells.

Citation: Tai A, Huber B. 2007. Viral Superantigens in Mice and Humans, p 59-75. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch4
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Figure 1.

The HERV-K18 provirus. The HERV-K18 provirus is mapped to the chromosomal region 1q23.1-24.1, within the SLAM family gene cluster. Specifically, it is located within the first intron of the cellular gene, but is in opposite transcriptional orientation. It is 9.2 kb and contains a functional ORF for the gene only. There are three alle-les of HERV-K18 env: K18.1, K18.2, and K18.3. Both K18.2 and K18.3 are predicted to encode a full-length Env protein of 560 amino acids. On the other hand, K18.1 is predicted to encode a truncated Env protein of 153 amino acids, as a result of a mutation converting the codon for tryptophan at position 154 into a stop codon. The three alleles are highly homologous to each other. The degree of homology between the two proviral LTRs encoding each allele is shown.

Citation: Tai A, Huber B. 2007. Viral Superantigens in Mice and Humans, p 59-75. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch4
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1. Acha-Orbea, H., and, H. R. MacDonald. 1995. Superantigens of mouse mammary tumor virus. Annu. Rev. Immunol. 13: 459486.
2. Akatsuka, H.,, K. Imanishi,, K. Inada,, H. Yamashita,, M. Yoshida, and, T. Uchiyama. 1994. Production of tumour necrosis factors by human T cells stimulated by a superantigen, toxic shock syndrome toxin-1. Clin. Exp. Immunol. 96: 422426.
3. Akolkar, P. N.,, N. Chirmule,, B. Gulwani-Akolkar,, S. Pahwa,, V. S. Kalyanaraman,, R. Pergolizzi,, S. Macphail, and, J. Silver. 1995. V beta-specific activation of T cells by the HIV glycoprotein gp 160. Scand. J. Immunol. 41: 487498.
4. Amariglio, N.,, A. Vonsover,, I. Hakim,, Y. Neumann,, Z. Mark,, F. Brok-Simoni,, I. Ben-Bassat, and, G. Rechavi. 1994. Immunoglobulin VH3-positive AIDS-related Burkitt’s lymphoma: a possible role for the HIV gp120 superantigen. Acta Haematol. 91: 103105.
5. Aubert, V.,, D. Schneeberger,, A. Sauty,, J. Winter,, P. Sperisen,, J. D. Aubert, and, F. Spertini. 2000. Induction of tumor necrosis factor alpha and interleukin-8 gene expression in bronchial epithelial cells by toxic shock syndrome toxin 1. Infect. Immun. 68: 120124.
6. Aude-Garcia, C.,, A. Attinger,, D. Housset,, H. R. MacDonald,, H. Acha-Orbea,, P. N. Marche, and, E. Jouvin-Marche. 2000. Pairing of Vbeta6 with certain Valpha2 family members prevents T cell deletion by Mtv-7 superantigen. Mol. Immunol. 37: 10051012.
7. Beezhold, D. H.,, G. K. Best,, P. F. Bonventre, and, M. Thompson. 1987. Synergistic induction of inter-leukin-1 by endotoxin and toxic shock syndrome toxin-1 using rat macrophages. Infect. Immun. 55: 28652869.
8. Beezhold, D. H.,, G. K. Best,, P. F. Bonventre, and, M. Thompson. 1989. Endotoxin enhancement of toxic shock syndrome toxin 1-induced secretion of interleukin 1 by murine macrophages. Rev. Infect. Dis. 11(Suppl. 1): S289S293.
9. Berberian, L.,, L. Goodglick,, T. J. Kipps, and, J. Braun. 1993. Immunoglobulin VH3 gene products: natural ligands for HIV gp120. Science 261: 15881591.
10. Berberian, L.,, J. Shukla,, R. Jefferis, and, J. Braun. 1994. Effects of HIV infection on VH3 (D12 idiotope) B cells in vivo. J Acquir. Immune Defic. Syndr. 7: 641646.
11. Beutner, U.,, B. McLellan,, E. Kraus, and, B. T. Huber. 1996. Lack of MMTV superantigen presentation in MHC class II-deficient mice. Cell. Immunol. 168: 141147.
12. Beutner, U.,, C. Rudy, and, B. T. Huber. 1992. Molecular characterization of Mls-1. Int. Rev. Immunol. 8: 279288.
13. Blackman, M. A., and, D. L. Woodland. 1996. Role of the T cell receptor alpha-chain in superantigen recognition. Immunol. Res. 15: 98113.
14. Blond, J. L.,, F. Beseme,, L. Duret,, O. Bouton,, F. Bedin,, H. Perron,, B. Mandrand, and, F. Mallet. 1999. Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. J. Virol. 73: 11751185.
15. Boldt-Houle, D. M.,, B. D. Jamieson,, G. M. Aldrovandi,, C. R. Rinaldo, Jr.,, G. D. Ehrlich, and, J. A. Zack. 1997. Loss of T cell receptor Vbeta repertoires in HIV type 1-infected SCID-hu mice. AIDS Res. Hum. Retroviruses 13: 125134.
16. Boldt-Houle, D. M.,, C. R. Rinaldo, Jr., and, G. D. Ehrlich. 1993. Random depletion of T cells that bear specific T cell receptor V beta sequences in AIDS patients. J. Leukoc. Biol. 54: 486491.
17. Boubou, M. I.,, A. Collette,, D. Voegtle,, D. Mazier,, P. A. Cazenave, and, S. Pied. 1999. T cell response in malaria pathogenesis: selective increase in T cells carrying the TCR V(beta)8 during experimental cerebral malaria. Int. Immunol. 11: 15531562.
18. Boutin, Y.,, D. Leitenberg,, X. Tao, and, K. Bottomly. 1997. Distinct biochemical signals characterize agonist- and altered peptide ligand-induced differentiation of naive CD4+ T cells into Th1 and Th2 subsets. J. Immunol. 159: 58025809.
19. Bowness, P.,, P. A. Moss,, H. Tranter,, J. I. Bell, and, A. J. McMichael. 1992. Clostridium perfringens enterotoxin is a superantigen reactive with human T cell receptors V beta 6.9 and V beta 22. J. Exp. Med. 176: 893896.
20. Boyer, V.,, L. R. Smith,, F. Ferre,, P. Pezzoli,, R. J. Trauger,, F. C. Jensen, and, D. J. Carlo. 1993. T cell receptor V beta repertoire in HIV-infection individuals: lack of evidence for selective V beta deletion. Clin. Exp. Immunol. 92: 437441.
21. Brandt, K.,, J. van der Bosch,, R. Fliegert, and, S. Gehring. 2002. TSST-1 induces Th1 or Th2 differentiation in naive CD4+ T cells in a dose- and APC-dependent manner. Scand. J. Immunol. 56: 572579.
22. Bras, A.,, L. Rodriguez-Borlado,, A. Gonzalez-Garcia, and, A. C. Martinez. 1997. Nitric oxide regulates clonal expansion and activation-induced cell death triggered by staphylococcal enterotoxin B. Infect. Immun. 65: 40304037.
23. Bravo de Alba, Y.,, P. N. Marche,, P. A. Cazenave,, I. Cloutier,, R. P. Sekaly, and, J. Thibodeau. 1997. V alpha domain modulates the multiple topologies of mouse T cell receptor V beta20/staphylococcal enterotoxins A and E complexes. Eur. J. Immunol. 27: 9299.
24. Buyalos, R. P.,, E. M. Rutanen,, E. Tsui, and, J. Halme. 1991. Release of tumor necrosis factor alpha by human peritoneal macrophages in response to toxic shock syndrome toxin-1. Obstet. Gynecol. 78: 182186.
25. Campbell, D. E., and, A. S. Kemp. 1997. Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in response to Staphylococcus aureus and staphylococcal superantigen in childhood atopic dermatitis. Clin. Exp. Immunol. 107: 392397.
26. Cardona, I. D.,, E. Goleva,, L. S. Ou, and, D. Y. Leung. 2006. Staphylococcal enterotoxin B inhibits regulatory T cells by inducing glucocorticoid-induced TNF receptor-related protein ligand on monocytes. J. Allergy Clin. Immunol. 117: 688695.
27. Choi, Y.,, P. Marrack, and, J. W. Kappler. 1992. Structural analysis of a mouse mammary tumor virus super-antigen. J. Exp. Med. 175: 847852.
28. Choi, Y. W.,, B. Kotzin,, L. Herron,, J. Callahan,, P. Marrack, and, J. Kappler. 1989. Interaction of Staphy-lococcus aureus toxin “superantigens” with human T cells. Proc. Natl. Acad. Sci. USA 86: 89418945.
29. Chwae, Y. J.,, I. H. Choi,, D. S. Kim,, E. C. Shin,, D. H. Kwon,, S. J. Kim, and, J. D. Kim. 1998. Clonal expansion of T-cells in measles. Immunol. Lett. 63: 147152.
30. Coppola, M. A.,, E. Flano,, P. Nguyen,, C. L. Hardy,, R. D. Cardin,, N. Shastri,, D. L. Woodland, and, M. A. Blackman. 1999. Apparent MHC-independent stimulation of CD8+ T cells in vivo during latent murine gammaherpesvirus infection. J. Immunol. 163: 14811489.
31. Cossarizza, A.,, C. Ortolani,, C. Mussini,, G. Guaraldi,, N. Mongiardo,, V. Borghi,, D. Barbieri,, E. Bellesia,, M. G. Franceschini,, B. De Rienzo, et al. 1995. Lack of selective V beta deletion in CD4+ or CD8+ T lymphocytes and functional integrity of T-cell repertoire during acute HIV syndrome. AIDS 9: 547553.
32. Cottrez, F.,, A. Capron, and, H. Groux. 1996. Selective CD4+ T cell deletion after specific activation in HIV-infected individuals; protection by anti-CD28 monoclonal antibodies. Clin. Exp. Immunol. 105: 3138.
33. Czarneski, J.,, J. C. Rassa, and, S. R. Ross. 2003. Mouse mammary tumor virus and the immune system. Immunol. Res. 27: 469480.
34. Dadaglio, G.,, S. Garcia,, L. Montagnier, and, M. L. Gougeon. 1994. Selective anergy of V beta 8+ T cells in human immunodeficiency virus-infected individuals. J. Exp. Med. 179: 413424.
35. Daly, K.,, P. Nguyen,, D. Hankley,, W. J. Zhang,, D. L. Woodland, and, M. A. Blackman. 1995. Contribution of the TCR alpha-chain to the differential recognition of bacterial and retroviral superantigens. J. Immunol. 155: 2734.
36. Denkers, E. Y.,, P. Caspar, and, A. Sher. 1994. Toxoplasma gondii possesses a superantigen activity that selectively expands murine T cell receptor V beta 5-bearing CD8+ lymphocytes. J. Exp. Med. 180: 985994.
37. Dewannieux, M.,, S. Blaise, and, T. Heidmann. 2005. Identification of a functional envelope protein from the HERV-K family of human endogenous retroviruses. J. Virol. 79: 1557315577.
38. Dobrescu, D.,, S. Kabak,, K. Mehta,, C. H. Suh,, A. Asch,, P. U. Cameron,, A. S. Hodtsev, and, D. N. Posnett. 1995. Human immunodeficiency virus 1 reservoir in CD4+ T cells is restricted to certain V beta subsets. Proc. Natl. Acad. Sci. USA 92: 55635567.
39. Dobrescu, D.,, B. Ursea,, M. Pope,, A. S. Asch, and, D. N. Posnett. 1995. Enhanced HIV1 replication in V beta 12 T cells due to human cytomegalovirus in monocytes: evidence for a putative herpesvirus superantigen. Cell 82: 753763.
40. Domiati-Saad, R., and, P. E. Lipsky. 1997. B cell superantigens: potential modifiers of the normal human B cell repertoire. Int. Rev. Immunol. 14: 309324.
41. Doyon, L.,, C. Simard,, R. P. Sekaly, and, P. Jolicoeur. 1996. Evidence that the murine AIDS defective virus does not encode a superantigen. J. Virol. 70: 19.
42. Du, C., and, S. Sriram. 2000. Induction of interleukin-12/p40 by superantigens in macrophages is mediated by activation of nuclear factor-kappaB. Cell. Immunol. 199: 5057.
43. Fast, D. J.,, B. J. Shannon,, M. J. Herriott,, M. J. Kennedy,, J. A. Rummage, and, R. W. Leu. 1991. Staphylococcal exotoxins stimulate nitric oxide-dependent murine macrophage tumoricidal activity. Infect. Immun. 59: 29872993.
44. Fingeroth, J. D.,, J. J. Weis,, T. F. Tedder,, J. L. Strominger,, P. A. Biro, and, D. T. Fearon. 1984. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc. Natl. Acad. Sci. USA 81: 45104514.
45. Firouzi, R.,, A. Rolland,, M. Michel,, E. Jouvin-Marche,, J. J. Hauw,, C. Malcus-Vocanson,, F. Lazarini,, L. Gebuhrer,, J. M. Seigneurin,, J. L. Touraine,, K. Sanhadji,, P. N. Marche, and, H. Perron. 2003. Multiple sclerosis-associated retrovirus particles cause T lymphocyte-dependent death with brain hemorrhage in humanized SCID mice model. J. Neurovirol. 9: 7993.
46. Foster, T. J. 2005. Immune evasion by staphylococci. Nat. Rev. Microbiol. 3: 948958.
47. Frade, R.,, M. Barel,, B. Ehlin-Henriksson, and, G. Klein. 1985. gp140, the C3d receptor of human B lymphocytes, is also the Epstein-Barr virus receptor. Proc. Natl. Acad. Sci. USA 82: 14901493.
48. Galelli, A.,, M. Delcourt,, M. C. Wagner,, W. Peumans, and, P. Truffa-Bachi. 1995. Selective expansion followed by profound deletion of mature V beta 8.3+ T cells in vivo after exposure to the superantigenic lectin Urtica dioica agglutinin. J. Immunol. 154: 26002611.
49. Galelli, A., and, P. Truffa-Bachi. 1993. Urtica dioica agglutinin. A superantigenic lectin from stinging nettle rhizome. J. Immunol. 151: 18211831.
50. Gayama, S.,, L. Doyon,, B. Vaupel,, R. P. Sekaly, and, O. Kanagawa. 1998. Induction of endogenous mammary tumor virus in lymphocytes infected with murine acquired immunodeficiency syndrome virus. Cell. Immunol. 187: 124130.
51. Gehring, S.,, M. Schlaak, and, J. van der Bosch. 1998. A new in vitro model for studying human T cell differentiation: T(H1)/T(H2) induction following activation by superantigens. J. Immunol. Methods 219: 8598.
52. Germain, R. N. 2002. T-cell development and the CD4-CD8 lineage decision. Nat. Rev. Immunol. 2: 309322.
53. Golovkina, T. V.,, I. Piazzon,, I. Nepomnaschy,, V. Buggiano,, M. de Olano Vela, and, S. R. Ross. 1997. Generation of a tumorigenic milk-borne mouse mammary tumor virus by recombination between endogenous and exogenous viruses. J. Virol. 71: 38953903.
54. Goodglick, L.,, N. Zevit,, M. S. Neshat, and, J. Braun. 1995. Mapping the Ig superantigen-binding site of HIV-1 gp120. J. Immunol. 155: 51515159.
55. Gougeon, M. L. 1995. Chronic activation of the immune system in HIV infection: contribution to T cell apoptosis and V beta selective T cell anergy. Curr. Top. Microbiol. Immunol. 200: 177193.
56. Hackett, S. P., and, D. L. Stevens. 1993. Superantigens associated with staphylococcal and streptococcal toxic shock syndrome are potent inducers of tumor necrosis factor-beta synthesis. J. Infect. Dis. 168: 232235.
57. Hardy, C. L.,, L. Lu,, P. Nguyen,, D. L. Woodland,, R. W. Williams, and, M. A. Blackman. 2001. Identification of quantitative trait loci controlling activation of TRBV4 CD8+ T cells during murine gamma-herpesvirus-induced infectious mononucleosis. Immunogenetics 53: 395400.
58. Hardy, C. L.,, S. L. Silins,, D. L. Woodland, and, M. A. Blackman. 2000. Murine gamma-herpesvirus infection causes V(beta)4-specific CDR3-restricted clonal expansions within CD8(+) peripheral blood T lymphocytes. Int. Immunol. 12: 11931204.
59. Hasuike, S.,, K. Miura,, O. Miyoshi,, T. Miyamoto,, N. Niikawa,, Y. Jinno, and, M. Ishikawa. 1999. Isolation and localization of an IDDMK1,2–22-related human endogenous retroviral gene, and identification of a CA repeat marker at its locus. J. Hum. Genet. 44: 343347.
60. Heaton, T.,, D. Mallon,, T. Venaille, and, P. Holt. 2003. Staphylococcal enterotoxin induced IL-5 stimulation as a cofactor in the pathogenesis of atopic disease: the hygiene hypothesis in reverse? Allergy 58: 252256.
61. Held, W.,, G. A. Waanders,, H. R. MacDonald, and, H. Acha-Orbea. 1994. MHC class II hierarchy of superantigen presentation predicts efficiency of infection with mouse mammary tumor virus. Int. Immunol. 6: 14031407.
62. Henne, E.,, W. H. Campbell, and, E. Carlson. 1991. Toxic shock syndrome toxin 1 enhances synthesis of endotoxin-induced tumor necrosis factor in mice. Infect. Immun. 59: 29292933.
63. Herman, A.,, J. W. Kappler,, P. Marrack, and, A. M. Pullen. 1991. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu. Rev. Immunol. 9: 745972.
64. Hirose, A.,, T. Ikejima, and, D. M. Gill. 1985. Established macrophagelike cell lines synthesize interleukin-1 in response to toxic shock syndrome toxin. Infect. Immun. 50: 765770.
65. Hogquist, K. A. 2001. Signal strength in thymic selection and lineage commitment. Curr. Opin. Immunol. 13: 225231.
66. Hoiden, I., and, G. Moller. 1996. CD8+ cells are the main producers of IL10 and IFN gamma after superantigen stimulation. Scand. J. Immunol. 44: 501505.
67. Hsiao, F. C.,, M. Lin,, A. Tai,, G. Chen, and, B. T. Huber. 2006. Cutting edge: Epstein-Barr Virus transacti-vates the HERV-K18 superantigen by docking to the human complement receptor 2 (CD21) on primary B cells. J. Immunol. 177: 20562060.
68. Hsu, P. N.,, P. Wolf Bryant,, N. Sutkowski,, B. McLellan,, H. L. Ploegh, and, B. T. Huber. 2001. Association of mouse mammary tumor virus superantigen with MHC class II during biosynthesis. J. Immunol. 166: 33093314.
69. Huber, B. T. 1995. The role of superantigens in virus infection. J. Clin. Immunol. 15: 22S25S.
70. Hugin, A. W.,, M. S. Vacchio, and, H. C. Morse III. 1991. A virus-encoded “superantigen” in a retrovirus-induced immunodeficiency syndrome of mice. Science 252: 424427.
71. Imberti, L.,, A. Sottini,, A. Bettinardi,, M. Puoti, and, D. Primi. 1991. Selective depletion in HIV infection of T cells that bear specific T cell receptor V beta sequences. Science 254: 860862.
72. Ito, Y.,, J. Abe,, K. Yoshino,, T. Takeda, and, T. Kohsaka. 1995. Sequence analysis of the gene for a novel superantigen produced by Yersinia pseudotuberculosis and expression of the recombinant protein. J. Immunol. 154: 58965906.
73. Iwashima, M. 2003. Kinetic perspectives of T cell antigen receptor signaling. A two-tier model for T cell full activation. Immunol. Rev. 191: 196210.
74. Jabara, H. H., and, R. S. Geha. 1996. The superantigen toxic shock syndrome toxin-1 induces CD40 ligand expression and modulates IgE isotype switching. Int. Immunol. 8: 15031510.
75. Jedrzkiewicz, S.,, G. Kataeva,, C. M. Hogaboam,, S. L. Kunkel,, R. M. Strieter, and, D. M. McKay. 1999. Superantigen immune stimulation evokes epithelial monocyte chemoattractant protein 1 and RANTES production. Infect. Immun. 67: 61986202.
76. Juompan, L.,, P. Lambin, and, M. Zouali. 1998. Selective deficit in antibodies specific for the superantigen binding site of gp120 in HIV infection. FASEB J. 12: 14731480.
77. 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. V beta-specific stimulation of human T cells by staphylococcal toxins. Science 244: 811813.
78. Karray, S., and, M. Zouali. 1997. Identification of the B cell superantigen-binding site of HIV-1 gp120. Proc. Natl. Acad. Sci. USA 94: 13561360.
79. Kobe, B.,, R. J. Center,, B. E. Kemp, and, P. Poumbourios. 1999. Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins. Proc. Natl. Acad. Sci. USA 96: 43194324.
80. Komanduri, K. V.,, M. D. Salha,, R. P. Sekaly, and, J. M. McCune. 1997. Superantigen-mediated deletion of specific T cell receptor V beta subsets in the SCID-hu Thy/Liv mouse is induced by staphylococcal entero-toxin B, but not HIV-1. J. Immunol. 158: 544549.
81. Krakauer, T. 1998. Interleukin-8 production by human monocytic cells in response to staphylococcal exotoxins is direct and independent of interleukin-1 and tumor necrosis factor-alpha. J. Infect. Dis. 178: 573577.
82. Krakauer, T. 1999. Induction of CC chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline. J. Leukoc. Biol. 66: 158164.
83. Lafon, M. 1997. Superantigen in rabies virus and its involvement in paralysis, p. 85102. In D. Y. M. Leung,, B. T. Huber, and, P. M. Schlievert(ed.), Superantigens: Molecular Biology, Immunology, and Relevance to Human Disease. Marcel Dekker, New York, N.Y.
84. Lafon, M.,, M. Lafage,, A. Martinez-Arends,, R. Ramirez,, F. Vuillier,, D. Charron,, V. Lotteau, and, D. Scott-Algara. 1992. Evidence for a viral superantigen in humans. Nature 358: 507510.
85. Lafon, M.,, D. Scott-Algara,, P. N. Marche,, P. A. Cazenave, and, E. Jouvin-Marche. 1994. Neonatal deletion and selective expansion of mouse T cells by exposure to rabies virus nucleocapsid superantigen. J. Exp. Med. 180: 12071215.
86. Lander, E. S.,, L. M. Linton,, B. Birren,, C. Nusbaum,, M. C. Zody,, J. Baldwin,, K. Devon,, K. Dewar,, M. Doyle,, W. FitzHugh,, R. Funke,, D. Gage,, K. Harris,, A. Heaford,, J. Howland,, L. Kann,, J. Lehoczky,, R. LeVine,, P. McEwan,, K. McKernan,, J. Meldrim,, J. P. Mesirov,, C. Miranda,, W. Morris,, J. Naylor,, C. Raymond,, M. Rosetti,, R. Santos,, A. Sheridan,, C. Sougnez,, N. Stange-Thomann,, N. Stojanovic,, A. Subramanian,, D. Wyman,, J. Rogers,, J. Sulston,, R. Ainscough,, S. Beck,, D. Bentley,, J. Burton,, C. Clee,, N. Carter,, A. Coulson,, R. Deadman,, P. Deloukas,, A. Dunham,, I. Dunham,, R. Durbin,, L. French,, D. Grafham,, S. Gregory,, T. Hubbard,, S. Humphray,, A. Hunt,, M. Jones,, C. Lloyd,, A. McMurray,, L. Matthews,, S. Mercer,, S. Milne,, J. C. Mullikin,, A. Mungall,, R. Plumb,, M. Ross,, R. Shownkeen,, S. Sims,, R. H. Waterston,, R. K. Wilson,, L. W. Hillier,, J. D. McPherson,, M. A. Marra,, E. R. Mardis,, L. A. Fulton,, A. T. Chinwalla,, K. H. Pepin,, W. R. Gish,, S. L. Chissoe,, M. C. Wendl,, K. D. Delehaunty,, T. L. Miner,, A. Delehaunty,, J. B. Kramer,, L. L. Cook,, R. S. Fulton,, D. L. Johnson,, P. J. Minx,, S. W. Clifton,, T. Hawkins,, E. Branscomb,, P. Predki,, P. Richardson,, S. Wenning,, T. Slezak,, N. Doggett,, J. F. Cheng,, A. Olsen,, S. Lucas,, C. Elkin,, E. Uberbacher,, M. Frazier, et al. 2001. Initial sequencing and analysis of the human genome. Nature 409: 860921.
87. Laurence, J.,, A. S. Hodtsev, and, D. N. Posnett. 1992. Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V beta expression. Nature 358: 255259.
88. 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: 72297237.
89. Lavoie, P. M.,, J. Thibodeau,, F. Erard, and, R. P. Sekaly. 1999. Understanding the mechanism of action of bacterial superantigens from a decade of research. Immunol. Rev. 168: 257269.
90. Lennon, G. P.,, J. E. Sillibourne,, E. Furrie,, M. J. Doherty, and, R. A. Kay. 2000. Antigen triggering selectively increases TCRBV gene transcription. J. Immunol. 165: 20202027.
91. Liu, B.,, Y. Wang,, S. M. Melana,, I. Pelisson,, V. Najfeld,, J. F. Holland, and, B. G. Pogo. 2001. Identification of a proviral structure in human breast cancer. Cancer Res. 61: 17541759.
92. Llewelyn, M.,, S. Sriskandan,, M. Peakman,, D. R. Ambrozak,, D. C. Douek,, W. W. Kwok,, J. Cohen, and, D. M. Altmann. 2004. HLA class II polymorphisms determine responses to bacterial superantigens. J. Immunol. 172: 17191726.
93. Marrack, P.,, M. Blackman,, E. Kushnir, and, J. Kappler. 1990. The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells. J. Exp. Med. 171: 455464.
94. Martinez-Arends, A.,, E. Astoul,, M. Lafage, and, M. Lafon. 1995. Activation of human tonsil lymphocytes by rabies virus nucleocapsid superantigen. Clin. Immunol. Immunopathol. 77: 177184.
95. McCarty, T. C.,, S. K. Chattopadhyay,, M. T. Scherer,, T. N. Fredrickson,, J. W. Hartley, and, H. C. Morse III. 1996. Endogenous Mtv-encoded superantigens are not required for development of murine AIDS. J. Virol. 70: 81488150.
96. Mi, S.,, X. Lee,, X. Li,, G. M. Veldman,, H. Finnerty,, L. Racie,, E. LaVallie,, X. Y. Tang,, P. Edouard,, S. Howes,, J. C. Keith, Jr., and, J. M. McCoy. 2000. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403: 785789.
97. Miyoshi-Akiyama, T.,, A. Abe,, H. Kato,, K. Kawahara,, H. Narimatsu, and, T. Uchiyama. 1995. DNA sequencing of the gene encoding a bacterial superantigen, Yersinia pseudotuberculosis-derived mitogen (YPM), and characterization of the gene product, cloned YPM. J. Immunol. 154: 52285234.
98. Muller, S., and, H. Kohler. 1997. B cell superantigens in HIV-1 infection. Int. Rev. Immunol. 14: 339349.
99. Neshat, M. N.,, L. Goodglick,, K. Lim, and, J. Braun. 2000. Mapping the B cell superantigen binding site for HIV-1 gp120 on a V(H)3 Ig. Int. Immunol. 12: 305312.
100. Niimi, N.,, W. Wajjwalku,, Y. Ando,, N. Nakamura,, M. Ueda, and, Y. Yoshikai. 1995. A novel V beta 2-specific endogenous mouse mammary tumor virus which is capable of producing a milk-borne exogenous virus. J. Virol. 69: 72697273.
101. Noel, C.,, S. Florquin,, M. Goldman, and, M. Y. Braun. 2001. Chronic exposure to superantigen induces regulatory CD4(+) T cells with IL-10-mediated suppressive activity. Int. Immunol. 13: 431439.
102. 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.
103. Perron, H.,, E. Jouvin-Marche,, M. Michel,, A. Ounanian-Paraz,, S. Camelo,, A. Dumon,, C. Jolivet-Reynaud,, F. Marcel,, Y. Souillet,, E. Borel,, L. Gebuhrer,, L. Santoro,, S. Marcel,, J. M. Seigneurin,, P. N. Marche, and, M. Lafon. 2001. Multiple sclerosis retrovirus particles and recombinant envelope trigger an abnormal immune response in vitro, by inducing polyclonal Vbeta16 T-lymphocyte activation. Virology 287: 321332.
104. Perron, H.,, F. Lazarini,, K. Ruprecht,, C. Pechoux-Longin,, D. Seilhean,, V. Sazdovitch,, A. Creange,, N. Battail-Poirot,, G. Sibai,, L. Santoro,, M. Jolivet,, J. L. Darlix,, P. Rieckmann,, T. Arzberger,, J. J. Hauw, and, H. Lassmann. 2005. Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions. J. Neurovi-rol. 11: 2333.
105. Posnett, D. N.,, S. Kabak,, D. Dobrescu, and, A. S. Hodtsev. 1995. The HIV-1 reservoir in distinct V beta subsets of CD4 T cells: evidence for a putative superantigen. J. Clin. Immunol. 15: 18S21S.
106. Posnett, D. N.,, S. Kabak,, A. S. Hodtsev,, E. A. Goldberg, and, A. Asch. 1993. T-cell antigen receptor V beta subsets are not preferentially deleted in AIDS. AIDS 7: 625631.
107. Rebai, N.,, G. Pantaleo,, J. F. Demarest,, C. Ciurli,, H. Soudeyns,, J. W. Adelsberger,, M. Vaccarezza,, R. E. Walker,, R. P. Sekaly, and, A. S. Fauci. 1994. Analysis of the T-cell receptor beta-chain variable-region (V beta) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbations of specific V beta segments in CD4+ T cells of the virus-positive twins. Proc. Natl. Acad. Sci. USA 91: 15291533.
108. Renard, M.,, P. F. Varela,, C. Letzelter,, S. Duquerroy,, F. A. Rey, and, T. Heidmann. 2005. Crystal structure of a pivotal domain of human syncytin-2, a 40 million years old endogenous retrovirus fusogenic envelope gene captured by primates. J. Mol. Biol. 352: 10291034.
109. Rink, L., and, H. Kirchner. 1992. Mycoplasma arthritidis-derived superantigen. Chem. Immunol. 55: 137145.
110. Rovira, P.,, M. Buckle,, J. P. Abastado,, W. J. Peumans, and, P. Truffa-Bachi. 1999. Major histocompati-bility class I molecules present Urtica dioica agglutinin, a superantigen of vegetal origin, to T lymphocytes. Eur. J. Immunol. 29: 15711580.
111. Ruprecht, K.,, K. Obojes,, V. Wengel,, F. Gronen,, K. S. Kim,, H. Perron,, J. Schneider-Schaulies, and, P. Rieckmann. 2006. Regulation of human endogenous retrovirus W protein expression by herpes simplex virus type 1: implications for multiple sclerosis. J. Neurovirol. 12: 6571.
112. Saul, F. A.,, P. Rovira,, G. Boulot,, E. J. Damme,, W. J. Peumans,, P. Truffa-Bachi, and, G. A. Bentley. 2000. Crystal structure of Urtica dioica agglutinin, a superantigen presented by MHC molecules of class I and class II. Structure 8: 593603.
113. Sawada, T.,, R. Pergolizzi,, K. Ito,, J. Silver,, C. Atkin,, B. C. Cole, and, M. D. Chang. 1995. Replacement of the DR alpha chain with the E alpha chain enhances presentation of Mycoplasma arthritidis superantigen by the human class II DR molecule. Infect. Immun. 63: 33673372.
114. Sen, N.,, W. J. Simmons,, R. M. Thomas,, G. Erianne,, D. J. Zhang,, N. S. Jaeggli,, C. Huang,, X. Xiong,, V. K. Tsiagbe,, N. M. Ponzio, and, G. J. Thorbecke. 2001. META-controlled env-initiated transcripts encoding superantigens of murine Mtv29 and Mtv7 and their possible role in B cell lymphomagenesis. J. Immunol. 166: 54225429.
115. Silverman, G. J.,, J. V. Nayak, and, A. La Cava. 1997. B-cell superantigens: molecular and cellular implications. Int. Rev. Immunol. 14: 259290.
116. Simmons, W. J.,, M. Simms,, R. Chiarle,, F. Mackay,, V. K. Tsiagbe,, J. Browning,, G. Inghirami, and, G. J. Thorbecke. 2001. Induction of germinal centers by MMTV encoded superantigen on B cells. Dev. Immunol. 8: 201211.
117. Soderquist, B.,, J. Kallman,, H. Holmberg,, T. Vikerfors, and, E. Kihlstrom. 1998. Secretion of IL-6, IL-8 and G-CSF by human endothelial cells in vitro in response to Staphylococcus aureus and staphylococcal exotoxins. APMIS 106: 11571164.
118. Soudeyns, H.,, J. P. Routy, and, R. P. Sekaly. 1994. Comparative analysis of the T cell receptor V beta repertoire in various lymphoid tissues from HIV-infected patients: evidence for an HIV-associated super-antigen. Leukemia 8(Suppl. 1): S95S97.
119. Stauffer, Y.,, S. Marguerat,, F. Meylan,, C. Ucla,, N. Sutkowski,, B. Huber,, T. Pelet, and, B. Conrad. 2001. Interferon-alpha-induced endogenous superantigen. A model linking environment and autoimmunity. Immunity 15: 591601.
120. Stuart, P. M.,, R. K. Munn,, E. DeMoll, and, J. G. Woodward. 1995. Characterization of human T-cell responses to Yersinia enterocolitica superantigen. Hum. Immunol. 43: 269275.
121. Surman, S.,, A. M. Deckhut,, M. A. Blackman, and, D. L. Woodland. 1994. MHC-specific recognition of a bacterial superantigen by weakly reactive T cells. J. Immunol. 152: 48934902.
122. Sutkowski, N.,, G. Chen,, G. Calderon, and, B. T. Huber. 2004. Epstein-Barr virus latent membrane protein LMP-2A is sufficient for transactivation of the human endogenous retrovirus HERV-K18 superantigen. J. Virol. 78: 78527860.
123. Sutkowski, N.,, B. Conrad,, D. A. Thorley-Lawson, and, B. T. Huber. 2001. Epstein-Barr virus transacti-vates the human endogenous retrovirus HERV-K18 that encodes a superantigen. Immunity 15: 579589.
124. Sutkowski, N., and, B. T. Huber. 2005. EBV induces an endogenous superantigen: implications for patho-genesis, p. 233262. In E. S. Robertson(ed.), Epstein-Barr Virus, 1st ed. Caister Academic Press, Norwich, United Kingdom.
125. Sutkowski, N.,, T. Palkama,, C. Ciurli,, R. P. Sekaly,, D. A. Thorley-Lawson, and, B. T. Huber. 1996. An Epstein-Barr virus-associated superantigen. J. Exp. Med. 184: 971980.
126. Tai, A. K.,, M. Lin,, F. Chang,, G. Chen,, F. Hsiao,, N. Sutkowski, and, B. T. Huber. 2006. Murine V3+ and V7+ T cell subsets are specific targets for the HERV-K18 Env superantigen. J. Immunol. 177: 31783184.
127. Takeda, T.,, K. Yoshino,, Y. Itoh,, J. Abe,, Y. Shimonishi, and, T. Kohsaka. 1995. Purification and gene cloning of a superantigen (YPM) produced by a patient strain of Yersinia pseudotuberculosis. Contrib. Microbiol. Immunol. 13: 331333.
128. Tao, X.,, S. Constant,, P. Jorritsma, and, K. Bottomly. 1997. Strength of TCR signal determines the cos-timulatory requirements for Th1 and Th2 CD4+ T cell differentiation. J. Immunol. 159: 59565963.
129. Tomonari, K., and, S. Fairchild. 1992. Positive and negative selection of Tcrb-V6+ T cells. Immunogenetics 36: 230237.
130. Townsley-Fuchs, J.,, M. S. Neshat,, D. H. Margolin,, J. Braun, and, L. Goodglick. 1997. HIV-1 gp120: a novel viral B cell superantigen. Int. Rev. Immunol. 14: 325338.
131. Trentin, L.,, R. Zambello,, M. Facco,, R. Sancetta,, A. Cerutti,, A. Milani,, C. Tassinari,, C. Crivellaro,, A. Cipriani,, C. Agostini, and, G. Semenzato. 1996. Skewing of the T-cell receptor repertoire in the lung of patients with HIV-1 infection. AIDS 10: 729737.
132. Tripp, R. A.,, A. M. Hamilton-Easton,, R. D. Cardin,, P. Nguyen,, F. G. Behm,, D. L. Woodland,, P. C. Do-herty, and, M. A. Blackman. 1997. Pathogenesis of an infectious mononucleosis-like disease induced by a murine gamma-herpesvirus: role for a viral superantigen? J. Exp. Med. 185: 16411650.
133. Venter, J. C.,, M. D. Adams,, E. W. Myers,, P. W. Li,, R. J. Mural,, G. G. Sutton,, H. O. Smith,, M. Yandell,, C. A. Evans,, R. A. Holt,, J. D. Gocayne,, P. Amanatides,, R. M. Ballew,, D. H. Huson,, J. R. Wortman,, Q. Zhang,, C. D. Kodira,, X. H. Zheng,, L. Chen,, M. Skupski,, G. Subramanian,, P. D. Thomas,, J. Zhang,, G. L. Gabor Miklos,, C. Nelson,, S. Broder,, A. G. Clark,, J. Nadeau,, V. A. McKusick,, N. Zinder,, A. J. Levine,, R. J. Roberts,, M. Simon,, C. Slayman,, M. Hunkapiller,, R. Bolanos,, A. Delcher,, I. Dew,, D. Fasulo,, M. Flanigan,, L. Florea,, A. Halpern,, S. Hannenhalli,, S. Kravitz,, S. Levy,, C. Mobarry,, K. Rein-ert,, K. Remington,, J. Abu-Threideh,, E. Beasley,, K. Biddick,, V. Bonazzi,, R. Brandon,, M. Cargill,, I. Chandramouliswaran,, R. Charlab,, K. Chaturvedi,, Z. Deng,, V. Di Francesco,, P. Dunn,, K. Eilbeck,, C. Evangelista,, A. E. Gabrielian,, W. Gan,, W. Ge,, F. Gong,, Z. Gu,, P. Guan,, T. J. Heiman,, M. E. Hig-gins,, R. R. Ji,, Z. Ke,, K. A. Ketchum,, Z. Lai,, Y. Lei,, Z. Li,, J. Li,, Y. Liang,, X. Lin,, F. Lu,, G. V. Merkulov,, N. Milshina,, H. M. Moore,, A. K. Naik,, V. A. Narayan,, B. Neelam,, D. Nusskern,, D. B. Rusch,, S. Salzberg,, W. Shao,, B. Shue,, J. Sun,, Z. Wang,, A. Wang,, X. Wang,, J. Wang,, M. Wei,, R. Wides,, C. Xiao,, C. Yan, et al. 2001. The sequence of the human genome. Science 291: 13041351.
134. Wallace, F. M.,, A. S. Mach,, A. M. Keller, and, J. A. Lindsay. 1999. Evidence for Clostridium perfringens enterotoxin (CPE) inducing a mitogenic and cytokine response in vitro and a cytokine response in vivo. Curr. Microbiol. 38: 96100.
135. Wang, Y.,, J. D. Jiang,, D. Xu,, Y. Li,, C. Qu,, J. F. Holland, and, B. G. Pogo. 2004. A mouse mammary tumor virus-like long terminal repeat superantigen in human breast cancer. Cancer Res. 64: 41054111.
136. Wang, Y.,, I. Pelisson,, S. M. Melana,, J. F. Holland, and, B. G. Pogo. 2001. Detection of MMTV-like LTR and LTR-env gene sequences in human breast cancer. Int. J. Oncol. 18: 10411044.
137. White, J.,, A. Herman,, A. M. Pullen,, R. Kubo,, J. W. Kappler, and, P. Marrack. 1989. The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 56: 2735.
138. Winslow, G. M.,, M. T. Scherer,, J. W. Kappler, and, P. Marrack. 1992. Detection and biochemical characterization of the mouse mammary tumor virus 7 superantigen (Mls-1a). Cell 71: 719730.
139. Zembowicz, A., and, J. R. Vane. 1992. Induction of nitric oxide synthase activity by toxic shock syndrome toxin 1 in a macrophage-monocyte cell line. Proc. Natl. Acad. Sci. USA 89: 20512055.


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Table 1.

Vβ specificity of exogenous and endogenous viral SAgs

Citation: Tai A, Huber B. 2007. Viral Superantigens in Mice and Humans, p 59-75. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch4

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