Combined ligand and receptor display

A method for selecting nucleic acid sequences encoding specific binding pairs comprising a first member and a second member, having specific binding affinity for each other, the method comprising:

• (a) providing a host microorganism which has been modified to prevent display of a surface molecule;
• (b) expressing in said host microorganism a nucleic acid encoding said surface molecule which is operably linked to a nucleic acid encoding a first member of said specific binding pair, said nucleic acid further encoding a first selectable marker which confers resistance to a first selection compound, wherein said first member is an antibody or functional fragment thereof having a specific binding property of said antibody, expression of said nucleic acid in said host microorganism resulting in the production of a first fusion protein comprising said surface molecule and said first member of said specific binding pair displayed on the surface of said host microorganism;
• (c) contacting the host microorganism of step (b) with at least one replicable genetic unit which expresses a nucleic acid encoding a second member of said specific binding pair, wherein said second member is an antigen, operably linked to a nucleic acid encoding a surface protein of said replicable genetic unit, said nucleic acid further encoding a second selectable marker which confers resistance to a second selection compound, expression of said nucleic acid in said replicable genetic unit resulting in the production of a second fusion protein displayed on the surface of said replicable genetic unit, said displayed second fusion protein comprising said second member of said specific binding pair produced by said replicable genetic unit having specific binding affinity for said first fusion protein displayed on the surface of host microorganisms of step (b), said contact of said displayed first and second binding pair members effectuating infection of said host microorganism by said replicable genetic unit, thereby transferring said nucleic acid of said replicable genetic unit into the host organism;
• (d) selecting infected host microorganisms containing both nucleic acids encoding said first and second specific binding pair members which grow in the presence of said first and second selection compounds;
• and
• (e) optionally, isolating said nucleic acids encoding said first and second binding pair members from said host microorganisms.