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Insertion of an immunodominant T helper cell epitope within the Group A Streptococcus M protein promotes an IFN-γ-dependent shift from a non-protective to a protective immune response

Emami, Shiva LU ; Rojas Converso, Thiago LU ; Persson, Jenny J. LU and Johansson-Lindbom, Bengt LU (2023) In Frontiers in Immunology 14.
Abstract

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... (More)

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-γ, and IFN-γ-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-γ-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.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antibodies, B cells, group A Streptococcus, IFN-γ, IgG2c, M protein, protection, T cells
in
Frontiers in Immunology
volume
14
article number
1241485
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85169351398
  • pmid:37654501
ISSN
1664-3224
DOI
10.3389/fimmu.2023.1241485
language
English
LU publication?
yes
id
dc25ee8e-e107-4900-a93e-f5ea7e94e30d
date added to LUP
2023-11-10 14:36:38
date last changed
2024-12-17 06:40:16
@article{dc25ee8e-e107-4900-a93e-f5ea7e94e30d,
  abstract     = {{<p>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-γ, and IFN-γ-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-γ-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.</p>}},
  author       = {{Emami, Shiva and Rojas Converso, Thiago and Persson, Jenny J. and Johansson-Lindbom, Bengt}},
  issn         = {{1664-3224}},
  keywords     = {{Antibodies; B cells; group A Streptococcus; IFN-γ; IgG2c; M protein; protection; T cells}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Insertion of an immunodominant T helper cell epitope within the Group A Streptococcus M protein promotes an IFN-γ-dependent shift from a non-protective to a protective immune response}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2023.1241485}},
  doi          = {{10.3389/fimmu.2023.1241485}},
  volume       = {{14}},
  year         = {{2023}},
}