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

MicrobiologyOpen

Jonas Lannergård¹  Bodil M. Kristensen¹  Mattias C. U. Gustafsson¹  Jenny J. Persson²  Anna Norrby-Teglund³  Margaretha Stålhammar-Carlemalm¹ 

[1] 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

关键词: Antibody escape;    group A Streptococcus;    immunodominance;    immunogenicity;    protease sensitivity;    sequence divergence;   

DOI  :  10.1002/mbo3.278

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

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