Immunoglobulin VH domains and beyond: design and selection of single-domain binding and targeting reagents

Identification of the smallest antibody fragment still capable of binding to antigen has progressed from full antibody molecules to Fab and recombinant single chain Fv fragments. Now, a further reduction to single domain binding proteins based upon immunoglobulin VH and VH-like domains offers exciting prospects in the development of novel immunotherapeutics and immunodiagnostics. Minimisation of the antigen-binding fragment to such small single-domain proteins offers the advantages of enhanced stability, and possibly access to a class of antigenic epitopes not generally recognised by conventional antibodies.