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Induction of human gamma interferon by structurally defined polypeptide fragments of group A streptococcal M protein
Abstract:
The presence of interferon (IFN) has been demonstrated previously (i) in fluids obtained from the middle ears of children with Streptococcus pneumoniae infections, (ii) from the serum of mice injected intraperitoneally with either S. pneumoniae or Streptococcus pyogenes, and (iii) from human lymphoid cell cultures treated with a variety of bacteria. In this study, we showed that highly purified peptic extracts of three different serotypes of group A streptococcal M protein (pep M5, pep M6, and pep M24) stimulated human peripheral leukocytes to produce IFN. IFN production was apparent by 10 h and peaked 24 h after exposure. Dose-response experiments indicated that IFN could be detected in cultures treated with concentrations of M protein as low as 6 micrograms/ml, whereas maximum IFN production occurred at a concentration of 200 micrograms/ml. The IFN had antigenic and physicochemical characteristics of IFN-gamma. Preliminary leukocyte fractionation studies revealed that the IFN-producing cell was a nonadherent lymphocyte with receptors for sheep erythrocytes (T cell). Rabbit antisera specific for these structurally defined polypeptide fragments of streptococcal M protein (pep M5, pep M6, and pep M24) blocked IFN induction by each of the polypeptides. The data suggest that the different serotypes of streptococcal M protein may induce IFN by a common structural determinant shared by each of the polypeptide fragments tested.
Insights
Streptococcal M protein fragments stimulate human leukocytes to produce interferon-gamma (IFN-γ). This immune response, mediated by T cells, suggests a common structural determinant across different M protein serotypes.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Interferon (IFN) presence is documented in Streptococcus pneumoniae infections and bacterial-treated cell cultures.
- Previous studies indicate IFN involvement in bacterial infections.
Purpose of the Study:
- To investigate the ability of streptococcal M protein fragments to stimulate IFN production.
- To characterize the type of IFN produced and the cells involved in its induction.
Main Methods:
- Exposure of human peripheral leukocytes to purified peptic extracts of streptococcal M protein (pep M5, pep M6, pep M24).
- Measurement of IFN production over time and at varying M protein concentrations.
- Characterization of IFN properties and identification of the producing cell type through leukocyte fractionation and antiserum blocking assays.
Main Results:
- Streptococcal M protein fragments induced IFN production in human leukocytes, peaking at 24 hours.
- IFN-gamma was identified as the primary type of IFN produced.
- The IFN-producing cells were identified as T lymphocytes.
- Antisera against M protein fragments blocked IFN induction, indicating specificity.
Conclusions:
- Structurally defined fragments of group A streptococcal M protein can induce IFN-gamma production.
- The induction appears to be mediated by T cells and involves a common structural determinant present in different M protein serotypes.