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Quantification of adaptive immune responses against protein binding interfaces in the streptococcal M1 protein

Torres-Sangiao, E LU orcid ; Happonen, L LU ; Heusel, M LU ; Palm, F LU ; Gueto-Tettay, C LU ; Malmström, L LU ; Shannon, O LU and Malmström, J LU orcid (2024) In Molecular and Cellular Proteomics
Abstract

Bacterial or viral antigens can contain subdominant protein regions that elicit weak antibody responses upon vaccination or infection although there is accumulating evidence that antibody responses against subdominant regions can enhance the protective immune response. One proposed mechanism for subdominant protein regions is binding of host proteins that prevent antibody production against epitopes hidden within the protein binding interfaces. Here, we used affinity-purification combined with quantitative mass spectrometry (AP-MS) to examine the level of competition between antigen-specific antibodies and host-pathogen protein interaction networks using the M1 protein from Streptococcus pyogenes as a model system. As most humans have... (More)

Bacterial or viral antigens can contain subdominant protein regions that elicit weak antibody responses upon vaccination or infection although there is accumulating evidence that antibody responses against subdominant regions can enhance the protective immune response. One proposed mechanism for subdominant protein regions is binding of host proteins that prevent antibody production against epitopes hidden within the protein binding interfaces. Here, we used affinity-purification combined with quantitative mass spectrometry (AP-MS) to examine the level of competition between antigen-specific antibodies and host-pathogen protein interaction networks using the M1 protein from Streptococcus pyogenes as a model system. As most humans have circulating antibodies against the M1 protein, we first used AP-MS to show that the M1 protein interspecies protein network formed with human plasma proteins is largely conserved in naïve mice. Immunizing mice with the M1 protein generated a time-dependent increase of anti-M1 antibodies. AP-MS analysis comparing the composition of the M1-plasma protein network from naïve and immunized mice showed a significant enrichment of 292 IgG peptides associated with 56 IgG chains in the immune mice. Despite the significant increase of bound IgGs, the levels of interacting plasma proteins were not significantly reduced in the immune mice. The results indicate that the antigen-specific polyclonal IgG against the M1 protein primarily targets epitopes outside the other plasma protein binding interfaces. In conclusion, this study demonstrates that AP-MS is a promising strategy to determine the relationship between antigen-specific antibodies and host-pathogen interaction networks that could be used to define subdominant protein regions of relevance for vaccine development.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Molecular and Cellular Proteomics
article number
100753
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:38527648
ISSN
1535-9484
DOI
10.1016/j.mcpro.2024.100753
language
English
LU publication?
yes
additional info
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
id
00689ad3-8e1d-4287-8af3-63062bd8ea6a
date added to LUP
2024-03-28 06:56:30
date last changed
2024-03-28 07:51:37
@article{00689ad3-8e1d-4287-8af3-63062bd8ea6a,
  abstract     = {{<p>Bacterial or viral antigens can contain subdominant protein regions that elicit weak antibody responses upon vaccination or infection although there is accumulating evidence that antibody responses against subdominant regions can enhance the protective immune response. One proposed mechanism for subdominant protein regions is binding of host proteins that prevent antibody production against epitopes hidden within the protein binding interfaces. Here, we used affinity-purification combined with quantitative mass spectrometry (AP-MS) to examine the level of competition between antigen-specific antibodies and host-pathogen protein interaction networks using the M1 protein from Streptococcus pyogenes as a model system. As most humans have circulating antibodies against the M1 protein, we first used AP-MS to show that the M1 protein interspecies protein network formed with human plasma proteins is largely conserved in naïve mice. Immunizing mice with the M1 protein generated a time-dependent increase of anti-M1 antibodies. AP-MS analysis comparing the composition of the M1-plasma protein network from naïve and immunized mice showed a significant enrichment of 292 IgG peptides associated with 56 IgG chains in the immune mice. Despite the significant increase of bound IgGs, the levels of interacting plasma proteins were not significantly reduced in the immune mice. The results indicate that the antigen-specific polyclonal IgG against the M1 protein primarily targets epitopes outside the other plasma protein binding interfaces. In conclusion, this study demonstrates that AP-MS is a promising strategy to determine the relationship between antigen-specific antibodies and host-pathogen interaction networks that could be used to define subdominant protein regions of relevance for vaccine development.</p>}},
  author       = {{Torres-Sangiao, E and Happonen, L and Heusel, M and Palm, F and Gueto-Tettay, C and Malmström, L and Shannon, O and Malmström, J}},
  issn         = {{1535-9484}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Molecular and Cellular Proteomics}},
  title        = {{Quantification of adaptive immune responses against protein binding interfaces in the streptococcal M1 protein}},
  url          = {{http://dx.doi.org/10.1016/j.mcpro.2024.100753}},
  doi          = {{10.1016/j.mcpro.2024.100753}},
  year         = {{2024}},
}