Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7749559
- author
- Lannergård, Jonas LU ; Kristensen, Bodil LU ; Gustafsson, Mattias LU ; Persson, Jenny J LU ; Norrby-Teglund, Anna ; Stålhammar-Carlemalm, Margaretha LU and Lindahl, Gunnar LU
- organization
- publishing date
- 2015
- 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
- pmid:26175306
- 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
- 2016-04-01 13:16:59
- date last changed
- 2022-03-13 23:07:48
@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}}, doi = {{10.1002/mbo3.278}}, volume = {{4}}, year = {{2015}}, }