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© 2015. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein
Author
Lannergård, Jonas 1 ; Kristensen, Bodil M 2 ; Gustafsson, Mattias C U 2 ; Persson, Jenny J 3 ; Anna Norrby‐Teglund 4 ; Margaretha Stålhammar‐Carlemalm 2 ; Lindahl, Gunnar 1 

 Department of Laboratory Medicine, Lund University, Lund, Sweden; Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg C, Denmark 
 Department of Laboratory Medicine, Lund University, Lund, Sweden 
 Department of Experimental Medical Science, Lund University, Lund, Sweden 
 Center for Infectious Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden 
Pages
774-789
Section
Original Research
Publication year
2015
Publication date
Oct 2015
Publisher
John Wiley & Sons, Inc.
e-ISSN
20458827
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2290241408
Copyright
© 2015. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.