Selection by phage display of llama conventional V(H) fragments with heavy chain antibody V(H)H properties

• Published in: Journal of immunological methods Vol. 263; no. 1-2; pp. 97 - 109
• Main Authors: Tanha, Jamshid, Dubuc, Ginette, Hirama, Tomoko, Narang, Saran A, MacKenzie, C Roger
• Format: Journal Article
• Language: English
• Published: Netherlands 01.05.2002
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Camelids, New World; DNA, Complementary; Humans; Immunoglobulin Fragments - genetics; Immunoglobulin Fragments - immunology; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - immunology; Immunoglobulin Variable Region - genetics; Immunoglobulin Variable Region - immunology; Molecular Sequence Data; Peptide Library; Sequence Homology, Amino Acid; Solubility; Temperature
• ISSN: 0022-1759

A llama single domain antibody (dAb) library designed and constructed to contain only heavy chain antibody variable domains (V(H)Hs) also contained a substantial number of typical conventional antibody heavy chain variable sequences (V(H)s). Panning the library against two carbohydrate-specific antibodies yielded anti-idiotypic dAbs and enriched solely for sequences from the V(H) subpopulation of the library. The conventional antibody origin of these V(H)s was confirmed by using oligonucleotide probes, specific for the enriched V(H)s, to identify the parental sequences in the message employed in library construction. Surprisingly, these V(H) dAbs, which are produced in high yield in Escherichia coli, are highly soluble, have excellent temperature stability profiles and do not display any aggregation tendencies. The very close similarity of these molecules to human V(H)s makes them potentially very useful as therapeutic dAbs.