Functional consequences of insertions and deletions in the complementarity-determining regions of human antibodies
Författare
Summary, in English
Insertions and deletions of nucleotides in the genes encoding the variable domains of antibodies are natural components of the hypermutation process, which may expand the available repertoire of hypervariable loop lengths and conformations. Although insertion of amino acids has also been utilized in antibody engineering, little is known about the functional consequences of such modifications. To investigate this further, we have introduced single-codon insertions and deletions as well as more complex modifications in the complementarity-determining regions of human antibody fragments with different specificities. Our results demonstrate that single amino acid insertions and deletions are generally well tolerated and permit production of stably folded proteins, often with retained antigen recognition, despite the fact that the thus modified loops carry amino acids that are disallowed at key residue positions in canonical loops of the corresponding length or are of a length not associated with a known canonical structure. We have thus shown that single-codon insertions and deletions can efficiently be utilized to expand structure and sequence space of the antigen-binding site beyond what is encoded by the germline gene repertoire.
Avdelning/ar
Publiceringsår
2002
Språk
Engelska
Sidor
45108-45114
Publikation/Tidskrift/Serie
Journal of Biological Chemistry
Volym
277
Issue
47
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Biochemistry and Molecular Biology
Ämne
- Immunology in the medical area
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1083-351X