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Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein: Implications for antigenic variation

Morfeldt, Eva; Berggård, Karin LU ; Persson, Jenny; Drakenberg, Torbjörn LU ; Johnsson, Eskil LU ; Lindahl, Erik; Linse, Sara LU and Lindahl, Gunnar LU (2001) In Journal of Immunology 167(7). p.3870-3877
Abstract
Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability. We studied this problem for a group of streptococcal M proteins in which the similar to 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP). Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form. This finding allowed direct characterization of the ligand-binding properties of... (More)
Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability. We studied this problem for a group of streptococcal M proteins in which the similar to 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP). Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form. This finding allowed direct characterization of the ligand-binding properties of isolated HVRs and permitted comparisons between different HV Rs in the absence of conserved parts of the M proteins. Affinity chromatography of human serum on immobilized peptides showed that they bound C4BP with high specificity and inhibition experiments indicated that different peptides bound to the same site in C4BP. Different C4BP-binding peptides did not exhibit any immunological cross-reactivity, but structural analysis suggested that they have similar folds. These data show that the HVR of streptococcal M protein can exhibit extreme variability in sequence and immunological properties while retaining a highly specific ligand-binding function. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
167
issue
7
pages
3870 - 3877
publisher
American Association of Immunologists
external identifiers
  • wos:000172392100042
  • scopus:0035478714
ISSN
1550-6606
language
English
LU publication?
yes
id
c880f481-1c1f-43f8-8425-7ea7f8919b06 (old id 1118656)
alternative location
http://www.jimmunol.org/cgi/reprint/167/7/3870
date added to LUP
2008-07-08 09:33:35
date last changed
2018-01-07 08:40:35
@article{c880f481-1c1f-43f8-8425-7ea7f8919b06,
  abstract     = {Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability. We studied this problem for a group of streptococcal M proteins in which the similar to 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP). Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form. This finding allowed direct characterization of the ligand-binding properties of isolated HVRs and permitted comparisons between different HV Rs in the absence of conserved parts of the M proteins. Affinity chromatography of human serum on immobilized peptides showed that they bound C4BP with high specificity and inhibition experiments indicated that different peptides bound to the same site in C4BP. Different C4BP-binding peptides did not exhibit any immunological cross-reactivity, but structural analysis suggested that they have similar folds. These data show that the HVR of streptococcal M protein can exhibit extreme variability in sequence and immunological properties while retaining a highly specific ligand-binding function.},
  author       = {Morfeldt, Eva and Berggård, Karin and Persson, Jenny and Drakenberg, Torbjörn and Johnsson, Eskil and Lindahl, Erik and Linse, Sara and Lindahl, Gunnar},
  issn         = {1550-6606},
  language     = {eng},
  number       = {7},
  pages        = {3870--3877},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein: Implications for antigenic variation},
  volume       = {167},
  year         = {2001},
}