Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein: Implications for antigenic variation
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1118656
- author
- Morfeldt, Eva ; Berggård, Karin LU ; Persson, Jenny LU ; Drakenberg, Torbjörn LU ; Johnsson, Eskil LU ; Lindahl, Erik ; Linse, Sara LU and Lindahl, Gunnar LU
- organization
- publishing date
- 2001
- type
- 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
- DOI
- 10.4049/jimmunol.167.7.3870
- language
- English
- LU publication?
- yes
- id
- c880f481-1c1f-43f8-8425-7ea7f8919b06 (old id 1118656)
- date added to LUP
- 2016-04-01 15:33:33
- date last changed
- 2022-01-28 05:54:36
@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}},
url = {{http://dx.doi.org/10.4049/jimmunol.167.7.3870}},
doi = {{10.4049/jimmunol.167.7.3870}},
volume = {{167}},
year = {{2001}},
}