A new subtraction technique for molecular cloning of rare antiviral antibody specificities from phage display libraries

The preparation of random combinatorial libraries exposed on the surface of phage provides a route for the selection of diverse high affinity human mo noclonal antibodies. However, in particular settings, the isolation of gene s coding for a rare antibody can be elusive because some epitopes are predo minant and because, in the case of impure antigens, the protein or any comp ound of interest can be present in relatively minimal amount, in this paper , we describe the successful utilization of a new strategy of "pre-adsorpti on" panning that allowed us to clone a rare human monoclonal antibody fragm ent and to access a different antibody repertoire. The procedure is easy, f ast, inexpensive, can be used together with other panning techniques and ca n be particularly useful in cloning antibodies against rare or unknown dete rminants.