Single domain antibodies: comparison of camel VH and camelised human VH domains.
The antigen binding sites of conventional antibodies are formed primarily by the hypervariable loops from both the heavy and the light chain variable domains. Functional antigen binding sites can however also be formed by heavy chain variable domains (VH) alone. In vivo, such binding sites have evolved in camels and camelids as part of antibodies, which consist only of two heavy chains and lack light chains. Analysis of the differences in amino acid sequence between the VHs of these camel heavy chain-only antibodies and VH domains from conventional human antibodies helped to design an altered human VH domain. This camelised VH proved, like the camel VH, to be a small, robust and efficient recognition unit formed by a single immunoglobulin (Ig) domain. Biochemical, structural and antigen binding characterisation properties of both camel VH domains and camelised human VH domains suggest that these can compete successfully with single chain variable domain (Fv) fragments from conventional antibodies in many applications. Of special importance in this respect is the use of such VH domains as enzyme inhibitors, for which they seem to be better suited than Fv fragments. This function appears to be closely related to their often very long third hypervariable loop, which is central for antigen recognition in their binding sites.
Riechmann
L
L
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK. lutz@mrc-lmb.cam.ac.uk
Muyldermans
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002162:Camelus; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011994:Recombinant Proteins