Nucleic Acids Research, 1991, Vol. 19, No. 15 4133-4137
© 1991
MOLECULAR BIOLOGY |
Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains
1Center for Protein Engineering Hills Road, Cambridge CB2 2QH, UK 2Cambridge Antibody Technology Ltd, Daly Research Laboratories, Babraham Hall Cambridge CB2 4AT, UK 4MRC Laboratory of Molecular Biology Hills Road, Cambridge CB2 2QH, UK 3CSIRO Division of Biomolecular Engineering 343 Royal Parade, Parkville, Victoria 3052, Australia
* To whom correspondence should be addressed
Received May 12, 1991. Revised June 17, 1991. Accepted June 17, 1991.
The display of proteins on the surface of phage offers a powerful means of selecting for rare genes encoding proteins with binding activities. Recently we found that antibody heavy and light chain variable (V) domains fused as a single polypeptide chain to a minor coat protein of filamentous phage fd, could be enriched by successive rounds of phage growth and panning with antigen. This allows the selection of antigen-binding domains directly from diverse libraries of V-genes. Now we show that heterodimeric Fab fragments can be assembled on the surface of the phage by linking one chain to the phage coat protein, and secreting the other into the bacterial periplasm. Furthermore by introducing an amber mutation between the antibody chain and the coat protein, we can either display the antibody on phage using supE strains of bacteria, or produce soluble Fab fragment using non-suppressor strains. The use of Fab fragments may offer advantages over single chain Fv fragments for construction of combinatorial libraries.
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