{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:48:38Z","timestamp":1790966918718,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2002,9,1]],"date-time":"2002-09-01T00:00:00Z","timestamp":1030838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The gene encoding streptococcal mitogenic exotoxin Z (SMEZ) was disrupted in Streptococcus pyogenes. Despite the presence of other superantigen genes, mitogenic responses in human and murine HLA-DQ transgenic cells were abrogated when cells were stimulated with supernatant from the smez\u2212 mutant compared with the parent strain. Remarkably, disruption of smez led to a complete inability to elicit cytokine production (TNF-\u03b1, lymphotoxin-\u03b1, IFN-\u03b3, IL-1 and -8) from human cells, when cocultured with streptococcal supernatants. The potent effects of SMEZ were apparent even though transcription and expression of SMEZ were barely detectable. Human V\u03b28+ T cell proliferation in response to S. pyogenes was SMEZ-dependent. Cells from HLA-DQ8 transgenic mice were 3 logs more sensitive to SMEZ-13 than cells from HLA-DR1 transgenic or wild-type mice. In the mouse, SMEZ targeted the human V\u03b28+ TCR homologue, murine V\u03b211, at the expense of other TCR T cell subsets. Expression of SMEZ did not affect bacterial clearance or survival from peritoneal streptococcal infection in HLA-DQ8 mice, though effects of SMEZ on pharyngeal infection are unknown. Infection did lead to a rise in V\u03b211+ T cells in the spleen which was partly reversed by disruption of the smez gene. Most strikingly, a clear rise in murine V\u03b24+ cells was seen in mice infected with the smez\u2212 mutant S. pyogenes strain, indicating a potential role for SMEZ as a repressor of cognate anti-streptococcal responses.<\/jats:p>","DOI":"10.4049\/jimmunol.169.5.2561","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T00:05:51Z","timestamp":1398125151000},"page":"2561-2569","source":"Crossref","is-referenced-by-count":69,"title":["The Bacterial Superantigen Streptococcal Mitogenic Exotoxin Z Is the Major Immunoactive Agent of\n                    <i>Streptococcus pyogenes<\/i>"],"prefix":"10.1093","volume":"169","author":[{"given":"Meera","family":"Unnikrishnan","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Faculty of Medicine, Imperial College School of Science, Technology, and Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M","family":"Altmann","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Faculty of Medicine, Imperial College School of Science, Technology, and Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Proft","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, University of Auckland , Auckland ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Wahid","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Faculty of Medicine, Imperial College School of Science, Technology, and Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Faculty of Medicine, Imperial College School of Science, Technology, and Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, University of Auckland , Auckland ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiranee","family":"Sriskandan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Faculty of Medicine, Imperial College School of Science, Technology, and Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,9,1]]},"reference":[{"key":"2026020209234688000_R1","first-page":"3828","volume-title":"Infect. Immun.","year":"1997"},{"key":"2026020209234688000_R2","first-page":"89","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026020209234688000_R3","first-page":"1765","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026020209234688000_R4","first-page":"4658","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026020209234688000_R5","first-page":"778","volume-title":"Mol. Microbiol.","year":"1999"},{"key":"2026020209234688000_R6","first-page":"2785","volume-title":"Microbiology","year":"2000"},{"key":"2026020209234688000_R7","first-page":"5495","volume-title":"Infect. Immun.","year":"1999"},{"key":"2026020209234688000_R8","first-page":"867","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026020209234688000_R9","first-page":"1765","volume-title":"Int. Immunol.","year":"1998"},{"key":"2026020209234688000_R10","first-page":"153","volume-title":"FEMS Microbiol. Lett.","year":"2000"},{"key":"2026020209234688000_R11","first-page":"3747","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020209234688000_R12","first-page":"285","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026020209234688000_R13","first-page":"2693","volume-title":"Eur. J. Immunol.","year":"1996"},{"key":"2026020209234688000_R14","first-page":"406","volume-title":"Immunology","year":"1997"},{"key":"2026020209234688000_R15","first-page":"139","volume-title":"Microbiol. Immunol.","year":"1994"},{"key":"2026020209234688000_R16","first-page":"2457","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020209234688000_R17","first-page":"209","volume-title":"FEMS Immunol. Med. Microbiol.","year":"2001"},{"key":"2026020209234688000_R18","first-page":"1381","volume-title":"Infect. Immun.","year":"2001"},{"key":"2026020209234688000_R19","first-page":"6711","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020209234688000_R20","first-page":"4141","volume-title":"Infect. Immun.","year":"2001"},{"key":"2026020209234688000_R21","first-page":"879","volume-title":"J. Infect. Dis.","year":"1992"},{"key":"2026020209234688000_R22","first-page":"3731","volume-title":"Infect. Immun.","year":"1994"},{"key":"2026020209234688000_R23","first-page":"69","volume-title":"Immunol. Rev.","year":"1992"},{"key":"2026020209234688000_R24","first-page":"232","volume-title":"J. Infect. Dis.","year":"1993"},{"key":"2026020209234688000_R25","first-page":"2430","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020209234688000_R26","first-page":"166","volume-title":"J. Infect. Dis.","year":"2001"},{"key":"2026020209234688000_R27","first-page":"157","volume-title":"J. Mol. Biol.","year":"2000"},{"key":"2026020209234688000_R28","first-page":"125","volume-title":"Scand. J. Infect. Dis.","year":"1995"},{"key":"2026020209234688000_R29","first-page":"1153","volume-title":"J. Exp. Med.","year":"1994"},{"key":"2026020209234688000_R30","first-page":"149","volume-title":"Immunol. Rev.","year":"1988"},{"key":"2026020209234688000_R31","first-page":"541","volume-title":"Immunity","year":"1997"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/169\/5\/2561\/62557737\/2561.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/169\/5\/2561\/62557737\/2561.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:33:31Z","timestamp":1770042811000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/169\/5\/2561\/8027678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,9,1]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2002,9,1]]},"published-print":{"date-parts":[[2002,9,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.169.5.2561","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2002,9]]},"published":{"date-parts":[[2002,9,1]]}}}