Recognition of antigens by single domain antibody fragments: the superfluous luxury of paired domains

The antigen-binding site of antibodies from vertebrates is formed by combin ing the variable domains of a heavy chain (VH) and a light chain (VL). Howe ver, antibodies from camels and Ilamas are an important exception to this i n that their sera contain, in addition, a unique kind of antibody that is f ormed by heavy chains only The antigen-binding site of these antibodies con sists of one single domain, referred to as VHH. This article reviews the mu tations and structural adaptations th at have ta ken place to reshape a VH of a VH-VL pair into a single-domain VHH with retention of a sufficient var iability, The VHH has a potent antigen-binding capacity and provides the ad vantage of interacting with novel epitopes that are inaccessible to convent ional VH-VL pairs.