Antibody domain mutants demonstrate autonomy of the antigen binding site.
We have constructed derivatives of a lambda I light chain-bearing anti-(4-hydroxy,3-nitrophenyl)acetyl (NP) antibody which have the V regions exchanged between heavy chains and light chains of the kappa or lambda I type. These antibodies are assembled and secreted normally, and bind haptenic and macromolecular ligands like the wild-type; similar results are obtained for monovalent heterodimers of VHCL and lambda I light chains. The observed independence of the binding site from the constant region context argues against a role of longitudinal interactions between constant and variable domains in antigen recognition, and therefore against cooperativity between binding sites.
Simon
T
T
Institut für Genetik, Universität zu Köln, FRG.
Rajewsky
K
K
D000818:Animals; D000936:Antigen-Antibody Complex; D001666:Binding Sites, Antibody / Q000235:genetics*; D002460:Cell Line; D006241:Haptens; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D007700:Kinetics; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology; D009154:Mutation; D010957:Plasmids; D011995:Recombination, Genetic; D014162:Transfection
D000936:Antigen-Antibody Complex; D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains