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Binding of human plasma proteins to Streptococcus pyogenes M protein determines the location of opsonic and non-opsonic epitopes

Sandin, Charlotta LU ; Carlsson, Fredric LU and Lindahl, Gunnar LU (2006) In Molecular Microbiology 59(1). p.20-30
Abstract
Antibodies directed against a pathogenic microorganism may recognize either protective or non-protective epitopes. Because antibodies elicited by a vaccine must be directed against protective epitopes, it is essential to understand the molecular properties that distinguish the two types of epitope. Here we analyse this problem for the antiphagocytic M protein of Streptococcus pyogenes, using the opsonizing capacity of antibodies to estimate their ability to confer protection in vivo. Our studies were focused on the M5 protein, which has three surface-exposed regions: the amino-terminal hypervariable region (HVR) and the B- and C-repeat regions. We first analysed the role of different M5 regions in phagocytosis resistance under non-immune... (More)
Antibodies directed against a pathogenic microorganism may recognize either protective or non-protective epitopes. Because antibodies elicited by a vaccine must be directed against protective epitopes, it is essential to understand the molecular properties that distinguish the two types of epitope. Here we analyse this problem for the antiphagocytic M protein of Streptococcus pyogenes, using the opsonizing capacity of antibodies to estimate their ability to confer protection in vivo. Our studies were focused on the M5 protein, which has three surface-exposed regions: the amino-terminal hypervariable region (HVR) and the B- and C-repeat regions. We first analysed the role of different M5 regions in phagocytosis resistance under non-immune conditions, employing chromosomal mutants expressing M5 proteins with internal deletions, and demonstrate that only the B-repeat region is essential for phagocytosis resistance. However, only antibodies to the HVR were opsonic. This apparent paradox could be explained by the ability of fibrinogen and albumin to specifically bind to the B- and C-repeats, respectively, causing inhibition of antibody binding under physiological conditions, while antibodies to the HVR could bind and promote deposition of complement. These data indicate that binding of human plasma proteins plays an important role in determining the location of opsonic and non-opsonic epitopes in streptococcal M protein. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Microbiology
volume
59
issue
1
pages
20 - 30
publisher
Wiley-Blackwell
external identifiers
  • pmid:16359315
  • wos:000233828700003
  • scopus:33645080955
ISSN
1365-2958
DOI
10.1111/j.1365-2958.2005.04913.x
language
English
LU publication?
yes
id
3b761461-b102-4d70-a133-4d0dd6db7ddc (old id 693845)
date added to LUP
2016-04-01 11:44:15
date last changed
2021-08-25 02:24:05
@article{3b761461-b102-4d70-a133-4d0dd6db7ddc,
  abstract     = {Antibodies directed against a pathogenic microorganism may recognize either protective or non-protective epitopes. Because antibodies elicited by a vaccine must be directed against protective epitopes, it is essential to understand the molecular properties that distinguish the two types of epitope. Here we analyse this problem for the antiphagocytic M protein of Streptococcus pyogenes, using the opsonizing capacity of antibodies to estimate their ability to confer protection in vivo. Our studies were focused on the M5 protein, which has three surface-exposed regions: the amino-terminal hypervariable region (HVR) and the B- and C-repeat regions. We first analysed the role of different M5 regions in phagocytosis resistance under non-immune conditions, employing chromosomal mutants expressing M5 proteins with internal deletions, and demonstrate that only the B-repeat region is essential for phagocytosis resistance. However, only antibodies to the HVR were opsonic. This apparent paradox could be explained by the ability of fibrinogen and albumin to specifically bind to the B- and C-repeats, respectively, causing inhibition of antibody binding under physiological conditions, while antibodies to the HVR could bind and promote deposition of complement. These data indicate that binding of human plasma proteins plays an important role in determining the location of opsonic and non-opsonic epitopes in streptococcal M protein.},
  author       = {Sandin, Charlotta and Carlsson, Fredric and Lindahl, Gunnar},
  issn         = {1365-2958},
  language     = {eng},
  number       = {1},
  pages        = {20--30},
  publisher    = {Wiley-Blackwell},
  series       = {Molecular Microbiology},
  title        = {Binding of human plasma proteins to Streptococcus pyogenes M protein determines the location of opsonic and non-opsonic epitopes},
  url          = {http://dx.doi.org/10.1111/j.1365-2958.2005.04913.x},
  doi          = {10.1111/j.1365-2958.2005.04913.x},
  volume       = {59},
  year         = {2006},
}