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

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Abstract

The variable domains of an antibody consist of a β-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 µM), 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 µM). Such ‘CDR replacement’ may offer a means of constructing human monoclonal antibodies from the corresponding mouse monoclonal antibodies.

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Authors and Affiliations

  1. Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge, CB2 2QH, UK

    Peter T. Jones, Paul H. Dear, Jefferson Foote, Michael S. Neuberger & Greg Winter

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  1. Peter T. Jones
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  2. Paul H. Dear
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  3. Jefferson Foote
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  4. Michael S. Neuberger
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  5. Greg Winter
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Jones, P., Dear, P., Foote, J. et al. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321, 522–525 (1986). https://doi.org/10.1038/321522a0

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  • DOI: https://doi.org/10.1038/321522a0

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