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Carl B

Carl Borrebaeck

Professor

Carl B

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

Author

  • P. Jirholt
  • L. Strandberg
  • B. Jansson
  • E. Krambovitis
  • Eskil Söderlind
  • Carl Borrebaeck
  • Roland Carlsson
  • L. Danielsson
  • Mats Ohlin

Summary, in English

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.

Department/s

  • Department of Immunotechnology

Publishing year

2001

Language

English

Pages

67-74

Publication/Series

Protein Engineering

Volume

14

Issue

1

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Immunology in the medical area

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

Status

Published

ISBN/ISSN/Other

  • ISSN: 1460-213X