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Cellular and biochemical responses of human T lymphocytes stimulated with streptococcal M proteins
M Kotb1, H S Courtney, J B Dale
1Veterans Administration Medical Center, Memphis, Tennessee 38104.
Abstract:
Purified group A streptococcal M proteins, pep M5 and pep M6, bearing heart cross-reactive epitopes were compared with pep M24, which lacks such epitopes, in their ability to induce functional differentiation of human T lymphocytes. Lymphocytes activated by pep M5 and pep M6 demonstrated cytotoxic activity against cultured heart cells, whereas pep M24-activated cells differentiated into suppressor T cells, which specifically blocked cytotoxic T lymphocytes against cultured human myocardial cells and not NK cell activity against K562 cells. Pep M5 and not pep M24 induced an increase in the number of CD4, 4B4, helper/inducer T cells. In addition, these M proteins appear to induce different biochemical changes in T lymphocytes. Both pep M5 and pep M24 induced the phosphorylation of a 35-kDa cytoplasmic protein; however, only pep M5 induced the phosphorylation of a 28-kDa membrane protein, primarily in CD4 T cells. These data indicate that the virulent M protein Ag of group A streptococci may exert their effect on the human immune system via different mechanisms. Determining these mechanisms and the biochemical pathways involved in T cell differentiation triggered by these Ag may be important in understanding the pathogenesis of post-streptococcal diseases.
Insights
Group A streptococcal M proteins with heart cross-reactive epitopes trigger T cell cytotoxicity, while others induce suppressor T cells. Understanding these distinct immune responses is crucial for post-streptococcal disease pathogenesis.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Group A Streptococcus (GAS) M proteins are key virulence factors.
- Some M proteins possess epitopes that cross-react with human heart tissue.
- The impact of M protein epitopes on human T lymphocyte differentiation is not fully understood.
Purpose of the Study:
- To compare the functional differentiation of human T lymphocytes induced by M proteins with and without heart cross-reactive epitopes.
- To investigate the biochemical changes in T lymphocytes following activation by different M proteins.
- To elucidate the mechanisms by which M proteins influence the human immune system and contribute to post-streptococcal diseases.
Main Methods:
- Purified M protein peptides (pep M5, pep M6, pep M24) were used to activate human T lymphocytes.
- Functional assays assessed cytotoxic activity against heart cells and T lymphocyte differentiation (cytotoxic T lymphocytes, suppressor T cells).
- Flow cytometry identified changes in T cell subsets (CD4, 4B4 helper/inducer T cells).
- Biochemical analysis measured protein phosphorylation (35-kDa cytoplasmic, 28-kDa membrane proteins).
Main Results:
- M proteins with heart cross-reactive epitopes (pep M5, pep M6) induced T lymphocytes with cytotoxic activity against heart cells.
- Pep M24, lacking these epitopes, induced suppressor T cells that inhibited cytotoxic T lymphocytes but not NK cell activity.
- Pep M5 increased CD4, 4B4 helper/inducer T cells, while pep M24 did not.
- Both M proteins induced phosphorylation of a 35-kDa cytoplasmic protein, but only pep M5 induced phosphorylation of a 28-kDa membrane protein in CD4 T cells.
Conclusions:
- Virulent M protein antigens of group A streptococci can induce distinct T lymphocyte differentiation pathways.
- These divergent mechanisms, involving different T cell subsets and biochemical changes, may be critical in the pathogenesis of post-streptococcal diseases.
- Further research into these pathways is essential for understanding and potentially preventing these conditions.