Structure and humanization of a rat monoclonal Fab to human interleukin-5

Abstract

The X-ray crystal structure of a rat monoclonal Fab JES1-39D10, raised against recombinant human interleukin-5, has been determined with the use of molecular replacement techniques and refined at 2.7 Å resolution by simulated annealing. The overall structure is similar to a murine Fab HyHEL-10 that is specific for hen egg white lysozyme. An interesting feature of the structure is the presence of leucine residues to support the H1 complementarity-determining region (CDR) loop. To our knowledge this is the first Fab crystal structure containing this unusual H1 loop support pattern. The activity of three humanized versions of 39D10 is explained by analysis of Fv interface residues and H1 support patterns of 39D10 and the human template HIL.