Establishment of a reliable dual-vector system for the phage display of antibody fragments

J Immunol Methods. 2008 Apr 20;333(1-2):24-37. doi: 10.1016/j.jim.2007.11.015. Epub 2007 Dec 31.

Abstract

To resolve some of the technical limitations in a phage-displayed Fab library, we have designed two dual-vector systems, DVS-I and DVS-II, composed of a set of replicon-compatible plasmid (pLA-1 or pLT-2) for producing soluble L chain fragments and phagemid (pHf1g3T-1 or pHf1g3A-2) for expressing Fd (V(H)+C(H1))-DeltapIII fusion molecules as well as a genotype-phenotype linkage. Compared to the DVS-I (pLA-1 and pHf1g3T-1), the DVS-II (pLT-2 and pHf1g3A-2) showed stable transformation efficiency regardless of the order of the vectors introduced into the host cells. In addition, expression of soluble Fab molecules with antigen-binding reactivity, recombinant phage titer and display level of functional Fab-DeltapIII on the phage progenies of the DVS-II were comparable with a conventional phage display system using a single phagemid vector. More importantly, the phage displaying target-specific Fab-DeltapIII molecules was successfully enriched by panning, which allows isolation of the pHf1g3A-2 phagemid encoding antigen-specific Fd molecules. We believe that the DVS-II may provide a valuable tool in the construction of a combinatorial phage-displayed Fab library with large diversity. Furthermore, it can be readily applied to isolation of desired antibody clones if L chain promiscuity of antibodies in determining antigen-binding specificity is considered, or in guided-selection or chain shuffling of mAbs of non-human origin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cloning, Molecular
  • DNA / chemistry
  • DNA / genetics
  • Electroporation / methods
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli / genetics
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology
  • Immunoglobulin Fab Fragments / genetics*
  • Immunoglobulin Fab Fragments / immunology
  • Peptide Library*
  • Plasmids / genetics*
  • Plasmids / immunology
  • Polymerase Chain Reaction

Substances

  • Immunoglobulin Fab Fragments
  • Peptide Library
  • DNA