| First Author | Emami S | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1241485 | PubMed ID | 37654501 |
| Mgi Jnum | J:340453 | Mgi Id | MGI:7527336 |
| Doi | 10.3389/fimmu.2023.1241485 | Citation | Emami S, et al. (2023) Insertion of an immunodominant T helper cell epitope within the Group A Streptococcus M protein promotes an IFN-gamma-dependent shift from a non-protective to a protective immune response. Front Immunol 14:1241485 |
| abstractText | The common pathogen Group A Streptococcus (GAS, Streptococcus pyogenes) is an extracellular bacterium that is associated with a multitude of infectious syndromes spanning a wide range of severity. The surface-exposed M protein is a major GAS virulence factor that is also target for protective antibody responses. In this study, we use a murine immunization model to investigate aspects of the cellular and molecular foundation for protective adaptive immune responses generated against GAS. We show that a wild type M1 GAS strain induces a non-protective antibody response, while an isogenic strain carrying the immunodominant 2W T helper cell epitope within the M protein elicits an immune response that is protective against the parental non-recombinant M1 GAS strain. Although the two strains induce total anti-GAS IgG levels of similar magnitude, only the 2W-carrying strain promotes elevated titers of the complement-fixing IgG2c subclass. Protection is dependent on IFN-gamma, and IFN-gamma-deficient mice show a specific reduction in IgG2c levels. Our findings suggest that inclusion of the 2W T cell epitope in the M protein confers essential qualitative alterations in the adaptive immune response against GAS, and that sparsity in IFN-gamma-promoting Th cell epitopes in the M protein may constitute an immune evasion mechanism, evolved to allow the pathogen to avoid attack by complement-fixing antibodies. |
