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T cell receptor V gene usage by human T cells stimulated with the superantigen streptococcal M protein
M A Tomai1, J A Aelion, M E Dockter
1Veteran's Administration Medical Center, Memphis, Tennessee 38104.
Abstract:
M proteins, the major virulence factor of group A streptococci, have been implicated in the pathogenesis of acute rheumatic fever (ARF) and other streptococcal related autoimmune diseases. A 22-kD fragment of M type 5 protein is a potent stimulant of human T cells and has recently been shown by our laboratory to belong to the newly designated family of superantigens. Using flow cytometry and the polymerase chain reaction, we demonstrate that this molecule reacts with subsets of human T cells expressing specific T cell receptor (TCR) V beta elements, namely V beta 2, 4, and 8. We employed similar techniques to analyze the TCR V alpha usage of pep M5-stimulated T cells. These studies revealed that the preferential usage of particular V alpha elements is not specific for the superantigen; rather, it may reflect the repertoire of the individual being tested. The expansion of a large number of T cells bearing specific TCR V beta sequences by M protein may account for its role in mediating the pathogenesis of post-streptococcal diseases. Furthermore, the preferential usage of TCR V alpha elements in certain individuals may be an important factor that predisposes them to development of self-reactivity.
Insights
Group A streptococci M proteins act as superantigens, stimulating T cells. This study shows M protein selectively activates T cells expressing specific T cell receptor V beta chains, potentially causing autoimmune diseases.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- M proteins are key virulence factors of Group A Streptococcus (GAS).
- GAS M proteins are implicated in acute rheumatic fever (ARF) and related autoimmune conditions.
- A specific M protein fragment (22-kD of M type 5) functions as a superantigen.
Purpose of the Study:
- To investigate the T cell receptor (TCR) usage in response to a streptococcal M protein superantigen.
- To determine if M protein superantigen exhibits specific T cell receptor V alpha element usage.
- To elucidate the role of TCR usage in M protein-mediated pathogenesis of post-streptococcal diseases.
Main Methods:
- Flow cytometry was used to analyze T cell populations.
- Polymerase chain reaction (PCR) was employed to assess T cell receptor gene expression.
- TCR V beta and V alpha usage was analyzed in T cells stimulated with M protein fragment (pep M5).
Main Results:
- The M protein fragment specifically stimulated T cells expressing TCR V beta 2, 4, and 8 elements.
- Preferential usage of specific TCR V alpha elements was observed but was individual-dependent, not superantigen-specific.
- A large expansion of T cells with specific TCR V beta sequences was induced by the M protein.
Conclusions:
- M protein-induced expansion of T cells with specific TCR V beta chains contributes to the pathogenesis of post-streptococcal autoimmune diseases.
- Individual variations in TCR V alpha usage may influence susceptibility to developing self-reactivity after streptococcal infections.