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The Hypervariable Region of Streptococcus pyogenes M Protein Escapes Antibody Attack by Antigenic Variation and Weak Immunogenicity.

På svenska

Author

  • Jonas Lannergård
  • Mattias Gustafsson
  • Johan Waldemarsson
  • Anna Norrby-Teglund
  • Margaretha Stålhammar-Carlemalm
  • Gunnar Lindahl

Summary, in English

Sequence variation of antigenic proteins allows pathogens to evade antibody attack. The variable protein commonly includes a hypervariable region (HVR), which represents a key target for antibodies and is therefore predicted to be immunodominant. To understand the mechanism(s) of antibody evasion, we analyzed the clinically important HVR-containing M proteins of the human pathogen Streptococcus pyogenes. Antibodies elicited by M proteins were directed almost exclusively against the C-terminal part and not against the N-terminal HVR. Similar results were obtained for mice and humans with invasive S. pyogenes infection. Nevertheless, only anti-HVR antibodies protected efficiently against infection, as shown by passive immunizations. The HVR fused to an unrelated protein elicited no antibodies, implying that it is inherently weakly immunogenic. These data indicate that the M protein HVR evades antibody attack not only through antigenic variation but also by weak immunogenicity, a paradoxical observation that may apply to other HVR-containing proteins.

Publishing year

2011

Language

English

Pages

147-157

Publication/Series

Cell Host and Microbe

Volume

10

Issue

2

Document type

Journal article

Publisher

Elsevier

Topic

  • Microbiology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 1934-6069