title: Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.
abstract: Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity.
authors.affiliation: Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8656 and Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639 Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Akiba
authors.affiliation: Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8656 and Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639 Japan Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8656 and Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639 Japan tsumoto@bioeng.t.u-tokyo.ac.jp.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
mesh_terms: D000937:Antigen-Antibody Reactions / Q000235:genetics / Q000276:immunology*; D006860:Hydrogen Bonding; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology*; D007700:Kinetics; D009154:Mutation; D013816:Thermodynamics
chemical_list: D007135:Immunoglobulin Variable Region
keywords: interaction; isothermal titration calorimetry; kinetics; protein structure; thermodynamics