Related Experiment Videos
Streptococcus pyogenes type 5 M protein is an antigen, not a superantigen, for human T cells
1School of Clinical Medical Sciences (Rheumatology), University of Newcastle upon Tyne, United Kingdom.
Abstract:
M proteins are coiled-coil dimers expressed on group A streptococcal cell surfaces. They have an important role in host antistreptococcal immunity and in poststreptococcal autoimmune sequelae. Controversy has arisen regarding whether type 5 M proteins are superantigenic for human T cells. To investigate this, we have produced and tested M5 in the form of two novel recombinant proteins. We found no evidence of superantigenicity using either recombinant whole M5 protein (rM5) or recombinant pep M5 protein (rpepM5) to activate peripheral blood mononuclear cells (PBMC) from healthy adult volunteers. Short-term, rM5-specific T-cell lines from different subjects were uniformly self-APC restricted and showed no consistent pattern of TCR V beta usage. A synthetic peptide of M5 residues 217-237 was found to contain epitope(s) recognized by some rM5-specific human T cells. PBMC responses to rM5 and rpepM5 in 3- and 7-day proliferation assays were characteristic of antigenic rather than superantigenic stimulation. We conclude that type 5 M protein activates human T cells as a conventional antigen.
Insights
Group A streptococcal M5 proteins do not act as superantigens for human T cells. Instead, M5 protein activates human T cells as a conventional antigen, challenging previous theories.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- M proteins on group A streptococcal surfaces are crucial for host immunity and autoimmune sequelae.
- Previous research has debated whether type 5 M proteins exhibit superantigenic properties in human T cells.
Purpose of the Study:
- To investigate the superantigenic potential of type 5 M proteins in human T cell activation.
- To determine the mechanism by which M5 protein interacts with human T cells.
Main Methods:
- Production and testing of two novel recombinant proteins: whole M5 protein (rM5) and pep M5 protein (rpepM5).
- Activation assays using peripheral blood mononuclear cells (PBMC) from healthy adult volunteers.
- Analysis of T-cell receptor (TCR) V beta usage and T-cell line restriction.
Main Results:
- No evidence of superantigenicity was found when using rM5 or rpepM5 to activate PBMC.
- rM5-specific T-cell lines demonstrated self-antigen-presenting cell (APC) restriction without consistent TCR V beta usage patterns.
- A synthetic peptide of M5 (residues 217-237) contained epitopes recognized by some human T cells.
- PBMC proliferation assays indicated antigenic, not superantigenic, stimulation by rM5 and rpepM5.
Conclusions:
- Type 5 M protein functions as a conventional antigen in activating human T cells.
- The findings resolve controversy regarding the superantigenic nature of M5 proteins.