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Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.

Lannergård, Jonas LU ; Kristensen, Bodil LU ; Gustafsson, Mattias LU ; Persson, Jenny J LU ; Norrby-Teglund, Anna; Stålhammar-Carlemalm, Margaretha LU and Lindahl, Gunnar LU (2015) In MicrobiologyOpen 4(5). p.774-789
Abstract
The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S. pyogenes-infected patients, infected mice, and... (More)
The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S. pyogenes-infected patients, infected mice, and immunized mice showed that both the HVR and the B repeat region elicited weak antibody responses, while the conserved carboxy-terminal part was immunodominant. Thus, we identified a correlation between sequence variability and weak immunogenicity for M protein regions. A potential explanation for the weak immunogenicity was provided by the demonstration that protease digestion selectively eliminated the HVR-B part from whole M protein-expressing bacteria. These data support a coherent model, in which the entire variable HVR-B part evades antibody attack, not only by sequence variability but also by weak immunogenicity resulting from protease attack. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
MicrobiologyOpen
volume
4
issue
5
pages
774 - 789
publisher
Wiley-Blackwell
external identifiers
  • pmid:26175306
  • wos:000363427500007
  • scopus:84944628148
ISSN
2045-8827
DOI
10.1002/mbo3.278
language
English
LU publication?
yes
id
f32b421f-f2ac-4253-b1c1-57717fcc779f (old id 7749559)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26175306?dopt=Abstract
date added to LUP
2015-08-08 19:39:44
date last changed
2017-10-01 04:05:47
@article{f32b421f-f2ac-4253-b1c1-57717fcc779f,
  abstract     = {The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S. pyogenes-infected patients, infected mice, and immunized mice showed that both the HVR and the B repeat region elicited weak antibody responses, while the conserved carboxy-terminal part was immunodominant. Thus, we identified a correlation between sequence variability and weak immunogenicity for M protein regions. A potential explanation for the weak immunogenicity was provided by the demonstration that protease digestion selectively eliminated the HVR-B part from whole M protein-expressing bacteria. These data support a coherent model, in which the entire variable HVR-B part evades antibody attack, not only by sequence variability but also by weak immunogenicity resulting from protease attack.},
  author       = {Lannergård, Jonas and Kristensen, Bodil and Gustafsson, Mattias and Persson, Jenny J and Norrby-Teglund, Anna and Stålhammar-Carlemalm, Margaretha and Lindahl, Gunnar},
  issn         = {2045-8827},
  language     = {eng},
  number       = {5},
  pages        = {774--789},
  publisher    = {Wiley-Blackwell},
  series       = {MicrobiologyOpen},
  title        = {Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.},
  url          = {http://dx.doi.org/10.1002/mbo3.278},
  volume       = {4},
  year         = {2015},
}