title: Tailored amino acid diversity for the evolution of antibody affinity.
abstract: Antibodies are a unique class of proteins with the ability to adapt their binding sites for high affinity and high specificity to a multitude of antigens. Many analyses have been performed on antibody sequences and structures to elucidate which amino acids have a predominant role in antibody interactions with antigens. These studies have generally not distinguished between amino acids selected for broad antigen specificity in the primary immune response and those selected for high affinity in the secondary immune response. By studying a large data set of affinity matured antibodies derived from in vitro directed evolution experiments, we were able to specifically highlight a subset of amino acids associated with affinity improvements. In a comparison of affinity maturations using either tailored or full amino acid diversification, the tailored approach was found to be at least as effective at improving affinity while requiring fewer mutagenesis libraries than the traditional method. The resulting sequence data also highlight the potential for further reducing amino acid diversity for high affinity binding interactions.
authors.affiliation: MedImmune Ltd., Cambridge, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: González-Muñoz
authors.forename: Evert
authors.initials: E
authors.lastname: Bokma
authors.forename: Desmond
authors.initials: D
authors.lastname: O'Shea
authors.forename: Kevin
authors.initials: K
authors.lastname: Minton
authors.forename: Martin
authors.initials: M
authors.lastname: Strain
authors.forename: Katherine
authors.initials: K
authors.lastname: Vousden
authors.forename: Christine
authors.initials: C
authors.lastname: Rossant
authors.forename: Lutz
authors.initials: L
authors.lastname: Jermutus
authors.forename: Ralph
authors.initials: R
authors.lastname: Minter
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000915:Antibody Affinity / Q000235:genetics; D000916:Antibody Diversity / Q000235:genetics; D001666:Binding Sites, Antibody / Q000235:genetics; D019295:Computational Biology; D015195:Drug Design; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D008958:Models, Molecular; D010850:Picornaviridae Infections / Q000276:immunology; D011487:Protein Conformation; D015202:Protein Engineering; D012229:Rhinovirus / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D007135:Immunoglobulin Variable Region; D057127:Single-Chain Antibodies