Du är här

Functional consequences of insertions and deletions in the complementarity-determining regions of human antibodies

Författare:
Publiceringsår: 2002
Språk: Engelska
Sidor: 45108-45114
Publikation/Tidskrift/Serie: Journal of Biological Chemistry
Volym: 277
Nummer: 47
Dokumenttyp: Artikel
Förlag: Amer Soc Biochemistry Molecular Biology Inc

Sammanfattning

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.

Disputation

Nyckelord

  • Biology and Life Sciences
  • Medicine and Health Sciences

Övriga

Published
Yes
  • ISSN: 0021-9258

Box 117, 221 00 LUND
Telefon 046-222 00 00 (växel)
Telefax 046-222 47 20
lu [at] lu [dot] se

LERU logotype U21 logotype

Fakturaadress: Box 188, 221 00 LUND
Organisationsnummer: 202100-3211
Om webbplatsen