title: Thermodynamic and kinetic aspects of antibody evolution during the immune response to hapten.
abstract: We determined thermodynamic and kinetic parameters for the antigen-antibody interaction using a group of anti-(4-hydroxy-3-nitrophenyl)acetyl monoclonal antibodies whose differences in amino acid sequences had arisen only from somatic hypermutation. These monoclonal antibodies were considered to have originated from a common ancestor clone and to represent progression along the affinity maturation pathway. The kinetic measurements showed that both association and dissociation rate constants of the antigen-antibody interaction decreased during maturation. Thermodynamic measurements revealed that an increase in affinity was obtained by an increase in entropy without any significant change in enthalpy. These results suggested that the mechanism for the antigen-antibody interaction shifted from a "zipper" type to a "lock-and-key" type during antibody evolution.
authors.affiliation: Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Sagawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Oda
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ishimura
authors.forename: Koji
authors.initials: K
authors.lastname: Furukawa
authors.forename: Takachika
authors.initials: T
authors.lastname: Azuma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000937:Antigen-Antibody Reactions / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002942:Circular Dichroism; D019143:Evolution, Molecular; D006241:Haptens / Q000276:immunology; D007700:Kinetics; D051379:Mice; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D017386:Sequence Homology, Amino Acid; D027041:Somatic Hypermutation, Immunoglobulin; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D006241:Haptens; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid