Replacing the complementarity-determining regions in a human antibody with those from a mouse

Nature. 1986 May 29-Jun 4;321(6069):522-5. doi: 10.1038/321522a0.

Abstract

The variable domains of an antibody consist of a beta-sheet framework with hypervariable regions (or complementarity-determining regions--CDRs) which fashion the antigen-binding site. Here we attempted to determine whether the antigen-binding site could be transplanted from one framework to another by grafting the CDRs. We substituted the CDRs from the heavy-chain variable region of mouse antibody B1-8, which binds the hapten NP-cap (4-hydroxy-3-nitrophenacetyl caproic acid; KNP-cap = 1.2 microM), for the corresponding CDRs of a human myeloma protein. We report that in combination with the B1-8 mouse light chain, the new antibody has acquired the hapten affinity of the B1-8 antibody (KNP-cap = 1.9 microM). Such 'CDR replacement' may offer a means of constructing human monoclonal antibodies from the corresponding mouse monoclonal antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Genes*
  • Humans
  • Immunoglobulin E / genetics
  • Immunoglobulin Variable Region / genetics*
  • Mice
  • Models, Molecular
  • Myeloma Proteins / genetics*
  • Plasmids
  • Protein Conformation
  • Species Specificity

Substances

  • Immunoglobulin Variable Region
  • Myeloma Proteins
  • Immunoglobulin E