Replacing the complementarity-determining regions in a human antibody with those from a mouse.
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.
P T
PT
Jones
P H
PH
Dear
J
J
Foote
M S
MS
Neuberger
G
G
Winter
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005796:Genes; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008958:Models, Molecular; D009194:Myeloma Proteins / Q000235:genetics*; D010957:Plasmids; D011487:Protein Conformation; D013045:Species Specificity
D007135:Immunoglobulin Variable Region; D009194:Myeloma Proteins; D007073:Immunoglobulin E