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.