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A central core structure in an antibody variable domain determines antigen specificity

Jirholt, P.; Strandberg, L.; Jansson, B.; Krambovitis, E.; Söderlind, Eskil LU ; Borrebaeck, Carl LU ; Carlsson, Roland LU ; Danielsson, L. and Ohlin, Mats LU (2001) In Protein Engineering 14(1). p.67-74
Abstract
Antibody binding sites provide an adaptable surface capable of interacting with essentially any molecular target. Using CDR shuffling, residues important for the assembly of mucin-1 specific paratopes were defined by random recombination of the complementarity determining regions derived from a set of mucin-1 specific clones, previously selected from an antibody fragment library. It was found that positions 33 and 50 in the heavy chain and 32, 34, 90, 91 and 96 in the light chain were conserved in many of the clones. These particular residues seem to be located centrally in the binding site as indicated by a structure model analysis. The importance of several of these conserved residues was supported by their presence in a mouse monoclonal... (More)
Antibody binding sites provide an adaptable surface capable of interacting with essentially any molecular target. Using CDR shuffling, residues important for the assembly of mucin-1 specific paratopes were defined by random recombination of the complementarity determining regions derived from a set of mucin-1 specific clones, previously selected from an antibody fragment library. It was found that positions 33 and 50 in the heavy chain and 32, 34, 90, 91 and 96 in the light chain were conserved in many of the clones. These particular residues seem to be located centrally in the binding site as indicated by a structure model analysis. The importance of several of these conserved residues was supported by their presence in a mouse monoclonal antibody with a known structure and the same epitope specificity. Several of these corresponding residues in the mouse monoclonal antibody are known to interact with the antigen. In conclusion, critical residues important for maintaining a human antigen-specific binding site during the process of in vitro antibody evolution were defined. Furthermore, an explanation for the observed restricted germline gene usage in certain antibody responses against protein epitopes is provided. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antibody evolution, complementarity determining region, mucin-1, paratope, phage display, DETERMINING REGION CDR, CHAIN FV ANTIBODIES, MONOCLONAL-ANTIBODIES, SOMATIC HYPERMUTATION, IMMUNE-RESPONSE, BINDING-SITE, IN-VITRO, GENES, REPERTOIRE, DIVERSITY
in
Protein Engineering
volume
14
issue
1
pages
67 - 74
publisher
Oxford University Press
external identifiers
  • wos:000168147500008
  • scopus:0035053451
ISSN
1460-213X
DOI
10.1093/protein/14.1.67
language
English
LU publication?
yes
id
8aaa1082-9acf-410d-a4ca-1f9c95bdde30 (old id 2376347)
date added to LUP
2012-03-23 09:37:22
date last changed
2018-01-07 05:22:27
@article{8aaa1082-9acf-410d-a4ca-1f9c95bdde30,
  abstract     = {Antibody binding sites provide an adaptable surface capable of interacting with essentially any molecular target. Using CDR shuffling, residues important for the assembly of mucin-1 specific paratopes were defined by random recombination of the complementarity determining regions derived from a set of mucin-1 specific clones, previously selected from an antibody fragment library. It was found that positions 33 and 50 in the heavy chain and 32, 34, 90, 91 and 96 in the light chain were conserved in many of the clones. These particular residues seem to be located centrally in the binding site as indicated by a structure model analysis. The importance of several of these conserved residues was supported by their presence in a mouse monoclonal antibody with a known structure and the same epitope specificity. Several of these corresponding residues in the mouse monoclonal antibody are known to interact with the antigen. In conclusion, critical residues important for maintaining a human antigen-specific binding site during the process of in vitro antibody evolution were defined. Furthermore, an explanation for the observed restricted germline gene usage in certain antibody responses against protein epitopes is provided.},
  author       = {Jirholt, P. and Strandberg, L. and Jansson, B. and Krambovitis, E. and Söderlind, Eskil and Borrebaeck, Carl and Carlsson, Roland and Danielsson, L. and Ohlin, Mats},
  issn         = {1460-213X},
  keyword      = {antibody evolution,complementarity determining region,mucin-1,paratope,phage display,DETERMINING REGION CDR,CHAIN FV ANTIBODIES,MONOCLONAL-ANTIBODIES,SOMATIC HYPERMUTATION,IMMUNE-RESPONSE,BINDING-SITE,IN-VITRO,GENES,REPERTOIRE,DIVERSITY},
  language     = {eng},
  number       = {1},
  pages        = {67--74},
  publisher    = {Oxford University Press},
  series       = {Protein Engineering},
  title        = {A central core structure in an antibody variable domain determines antigen specificity},
  url          = {http://dx.doi.org/10.1093/protein/14.1.67},
  volume       = {14},
  year         = {2001},
}