The bacterial superantigen streptococcal mitogenic exotoxin Z is the major immunoactive agent of Streptococcus pyogenes.

Abstract

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(-) mutant compared with the parent strain. Remarkably, disruption of smez led to a complete inability to elicit cytokine production (TNF-alpha, lymphotoxin-alpha, IFN-gamma, 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 Vbeta8(+) 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 Vbeta8(+) TCR homologue, murine Vbeta11, 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 Vbeta11(+) T cells in the spleen which was partly reversed by disruption of the smez gene. Most strikingly, a clear rise in murine Vbeta4(+) cells was seen in mice infected with the smez(-) mutant S. pyogenes strain, indicating a potential role for SMEZ as a repressor of cognate anti-streptococcal responses.

• Authors: Meera Unnikrishnan, Daniel M Altmann, Thomas Proft, Faisal Wahid, Jonathan Cohen, John D Fraser, Shiranee Sriskandan
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 5 Pg. 2561-9 (Sep 01 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12193726 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Bacterial Toxins
• Cytokines
• Exotoxins
• HLA-DQ Antigens
• HLA-DQ8 antigen
• HLA-DR1 Antigen
• Mitogens
• Receptors, Antigen, T-Cell, alpha-beta
• Superantigens
• mitogenic exotoxin Z protein, Streptococcus

Topics

• Acute Disease
• Animals
• Antigens, Bacterial (biosynthesis, genetics, immunology)
• Bacterial Toxins (biosynthesis, genetics, immunology)
• Blotting, Southern
• Cell Division (immunology)
• Cell Line
• Cells, Cultured
• Cytokines (biosynthesis, metabolism)
• Exotoxins (biosynthesis, genetics, immunology, metabolism)
• Gene Expression Regulation (immunology)
• Genotype
• HLA-DQ Antigens (biosynthesis, genetics)
• HLA-DR1 Antigen (biosynthesis, genetics)
• Humans
• Leukocytes, Mononuclear (immunology, metabolism)
• Lymphocyte Activation (immunology)
• Lymphocyte Count
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mitogens (biosynthesis, genetics, immunology, metabolism)
• Peritonitis (immunology, microbiology)
• Polymerase Chain Reaction (methods)
• Receptors, Antigen, T-Cell, alpha-beta (biosynthesis)
• Spleen (cytology, immunology, microbiology)
• Streptococcal Infections (immunology, microbiology)
• Streptococcus pyogenes (genetics, growth & development, immunology, metabolism)
• Superantigens (genetics, immunology)
• T-Lymphocyte Subsets (cytology, immunology, metabolism, pathology)
• Transcription, Genetic (immunology)