In vitro molecular evolution of antibody genes mimicking receptor revision.
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.
Ellmark
Peter
P
Department of Immunotechnology, Lund University, P.O. Box 7031, S-220 07, Lund, Sweden.
Esteban
Olga
O
Furebring
Christina
C
Malmborg Hager
Ann-Christin
AC
Ohlin
Mats
M
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*
D000906:Antibodies; D022801:Complementarity Determining Regions; D019151:Peptide Library; D011947:Receptors, Antigen, B-Cell