Advanced

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

Lannergård, Jonas LU ; Gustafsson, Mattias LU ; Waldemarsson, Johan LU ; Norrby-Teglund, Anna; Stålhammar-Carlemalm, Margaretha LU and Lindahl, Gunnar LU (2011) In Cell Host and Microbe 10(2). p.147-157
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Host and Microbe
volume
10
issue
2
pages
147 - 157
publisher
Elsevier
external identifiers
  • wos:000295185900009
  • pmid:21843871
  • scopus:80051876563
ISSN
1934-6069
DOI
10.1016/j.chom.2011.06.011
language
English
LU publication?
yes
id
eea846f7-d2f0-461d-99ad-c0e0feacd009 (old id 2151060)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21843871?dopt=Abstract
date added to LUP
2011-09-04 14:39:33
date last changed
2017-10-01 04:55:50
@article{eea846f7-d2f0-461d-99ad-c0e0feacd009,
  abstract     = {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.},
  author       = {Lannergård, Jonas and Gustafsson, Mattias and Waldemarsson, Johan and Norrby-Teglund, Anna and Stålhammar-Carlemalm, Margaretha and Lindahl, Gunnar},
  issn         = {1934-6069},
  language     = {eng},
  number       = {2},
  pages        = {147--157},
  publisher    = {Elsevier},
  series       = {Cell Host and Microbe},
  title        = {The Hypervariable Region of Streptococcus pyogenes M Protein Escapes Antibody Attack by Antigenic Variation and Weak Immunogenicity.},
  url          = {http://dx.doi.org/10.1016/j.chom.2011.06.011},
  volume       = {10},
  year         = {2011},
}