Antibody redesign by chain shuffling from random combinatorial immunoglobulin libraries.
A number of experiments on the shuffling of heavy and light chains from antibodies of defined specificity for the transition-state analogue hapten nitrophenyl phosphonamidate are described. The experiments report on the promiscuity of heavy and light chains in binding antigen and the feasibility of antibody redesign by this shuffling process. The concepts of incestuous and extraclonal promiscuous association are described. Shuffling opens the possibility of generating panels of antibodies with related specificity but of distinct idiotypic composition that may have significance in the use of human monoclonal antibodies in therapy.
Kang
A S
AS
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Jones
T M
TM
Burton
D R
DR
D000818:Animals; D000916:Antibody Diversity / Q000235:genetics*; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics; D004247:DNA / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015723:Gene Library; D005803:Genes, Immunoglobulin; D006241:Haptens / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data
D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D004247:DNA