title: In vitro molecular evolution of antibody genes mimicking receptor revision.
abstract: Antibody evolution in vivo proceeds mainly by stepwise improvements, accomplished by single base pair substitutions. Lately, receptor revision, i.e. exchange of large parts of the V gene for another sequence, has been suggested to provide a complementary route for affinity maturation. By employing a receptor revision like evolution process in vitro using combinatorial libraries and phage display selection, we demonstrate here that maturation of a clone may preferentially proceed through exchange of a large gene segment rather than via minor sequence changes. These modifications of a CD40-specific human antibody fragment outline how receptor revision like events may provide an advantage to a particular clonotype put under selective pressure.
authors.affiliation: Department of Immunotechnology, Lund University, P.O. Box 7031, S-220 07, Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Ellmark
authors.forename: Olga
authors.initials: O
authors.lastname: Esteban
authors.forename: Christina
authors.initials: C
authors.lastname: Furebring
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Malmborg Hager
authors.forename: Mats
authors.initials: M
authors.lastname: Ohlin
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry / Q000235:genetics*; D000918:Antibody Specificity; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D019151:Peptide Library; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*
chemical_list: D000906:Antibodies; D022801:Complementarity Determining Regions; D019151:Peptide Library; D011947:Receptors, Antigen, B-Cell