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Published on: January 7, 2019
Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation
Lisa I Påhlman1, Anders I Olin, Jessica Darenberg
1Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden.
Abstract:
Streptococcus pyogenes of the M1 serotype is commonly associated with large outbreaks of invasive streptococcal infections and development of streptococcal toxic shock syndrome (STSS). The pathogenesis behind these infections is believed to involve bacterial superantigens that induce potent inflammatory responses, but the reason why strains of the M1 serotype are over-represented in STSS is still not understood. In the present investigation, we show that a highly purified soluble form of the M1 protein from S. pyogenes, which lacks the membrane-spanning region, is a potent inducer of T cell proliferation and release of Th1 type cytokines. M1 protein-evoked T cell proliferation was HLA class II-dependent but not MHC-restricted, did not require intracellular processing and was Vbeta-restricted. Extensive mass spectrometry studies indicated that there were no other detectable proteins in the preparation. Taken together, our data demonstrate that soluble M1 protein is a novel streptococcal superantigen, which likely contributes to the excessive T cell activation and hyperinflammatory response seen in severe invasive streptococcal infections.
Insights
Streptococcus pyogenes M1 protein acts as a superantigen, driving T cell activation and inflammatory responses. This finding helps explain the severity of invasive streptococcal infections and toxic shock syndrome.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Streptococcus pyogenes M1 serotype causes invasive infections and toxic shock syndrome (STSS).
- Bacterial superantigens are implicated in pathogenesis, but M1 serotype's role is unclear.
Purpose of the Study:
- To investigate the role of soluble M1 protein from S. pyogenes in T cell activation and cytokine release.
- To determine if M1 protein functions as a superantigen in severe streptococcal infections.
Main Methods:
- Purification of soluble M1 protein from S. pyogenes.
- Assessing T cell proliferation and Th1 cytokine release.
- Mass spectrometry to confirm protein purity.
- Investigating HLA class II dependence, MHC restriction, processing requirements, and Vbeta restriction.
Main Results:
- Soluble M1 protein potently induced T cell proliferation and Th1 cytokine release.
- M1 protein-evoked T cell activation was HLA class II-dependent but not MHC-restricted.
- Activation did not require intracellular processing and was Vbeta-restricted.
- Mass spectrometry confirmed the absence of other detectable proteins.
Conclusions:
- Soluble M1 protein from S. pyogenes is identified as a novel superantigen.
- M1 protein likely contributes to excessive T cell activation and hyperinflammation in severe invasive streptococcal infections.
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