Functional consequences of insertions and deletions in the complementarity-determining regions of human antibodies
Lantto, Johan LU and Ohlin, Mats LU
(2002)
In Journal of Biological Chemistry
277(47).
p.45108-45114
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/322822
- author
- Lantto, Johan
LU
and Ohlin, Mats
LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 277
- issue
- 47
- pages
- 45108 - 45114
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000179404800067
- scopus:0037160031
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M208401200
- language
- English
- LU publication?
- yes
- id
- fdee3e00-4bd0-4d2c-9086-dc2f3318f703 (old id 322822)
- date added to LUP
- 2016-04-01 12:28:39
- date last changed
- 2022-01-27 05:37:38
@article{fdee3e00-4bd0-4d2c-9086-dc2f3318f703,
abstract = {{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.}},
author = {{Lantto, Johan and Ohlin, Mats}},
issn = {{1083-351X}},
language = {{eng}},
number = {{47}},
pages = {{45108--45114}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Functional consequences of insertions and deletions in the complementarity-determining regions of human antibodies}},
url = {{http://dx.doi.org/10.1074/jbc.M208401200}},
doi = {{10.1074/jbc.M208401200}},
volume = {{277}},
year = {{2002}},
}