Light chain shuffling of a high affinity antibody results in a drift in epitope recognition
(1996) In Molecular Immunology 33(1). p.47-56- Abstract
- Human polyclonal and monoclonal antibodies against pathogens and toxins are potentially useful in the treatment of various diseases. A number of human monoclonal antibodies with protective capacity in vitro have been established by conventional hybridoma technology. However, with the development of phage-display technology, the possibility of specifically tailoring antigen-binding properties has improved substantially. We show here that the reactivity of a high affinity, virus-neutralizing human antibody against the AD-2 epitope of cytomegalovirus gB can be modified by introducing other Vkappa sequences together with the original VH sequence. The fine specificity, as determined by the requirement of particular amino acid residues in the... (More)
- Human polyclonal and monoclonal antibodies against pathogens and toxins are potentially useful in the treatment of various diseases. A number of human monoclonal antibodies with protective capacity in vitro have been established by conventional hybridoma technology. However, with the development of phage-display technology, the possibility of specifically tailoring antigen-binding properties has improved substantially. We show here that the reactivity of a high affinity, virus-neutralizing human antibody against the AD-2 epitope of cytomegalovirus gB can be modified by introducing other Vkappa sequences together with the original VH sequence. The fine specificity, as determined by the requirement of particular amino acid residues in the epitope, is shifted in these new antibody fragments. It was also evident that the VH/Vkappa pairing was not promiscuous, since antibody fragments selected by phage display retained light chain sequences very similar to the original hybridoma-derived light chain, proving that a high affinity interaction was very dependent on a co-operativity between both variable domains. These findings show that phage display technology might modify the binding properties of pre-existing, high affinity antibodies. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1110672
- author
- Ohlin, Mats LU ; Owman, Henrik LU ; Mach, Michael and Borrebaeck, Carl LU
- organization
- publishing date
- 1996
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cytomegalovirus, human monoclonal antibody, glycoprotein B (gB), phage-display technology, antibody specificity
- in
- Molecular Immunology
- volume
- 33
- issue
- 1
- pages
- 47 - 56
- publisher
- Pergamon Press Ltd.
- external identifiers
-
- pmid:8604223
- scopus:0029981792
- ISSN
- 1872-9142
- DOI
- 10.1016/0161-5890(95)00123-9
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Reconstructive Surgery (013240300), Department of Immunotechnology (011029300)
- id
- c8596726-4a88-4b96-98c6-84ad97e4988c (old id 1110672)
- date added to LUP
- 2016-04-01 16:01:24
- date last changed
- 2022-05-16 02:32:57
@article{c8596726-4a88-4b96-98c6-84ad97e4988c, abstract = {{Human polyclonal and monoclonal antibodies against pathogens and toxins are potentially useful in the treatment of various diseases. A number of human monoclonal antibodies with protective capacity in vitro have been established by conventional hybridoma technology. However, with the development of phage-display technology, the possibility of specifically tailoring antigen-binding properties has improved substantially. We show here that the reactivity of a high affinity, virus-neutralizing human antibody against the AD-2 epitope of cytomegalovirus gB can be modified by introducing other Vkappa sequences together with the original VH sequence. The fine specificity, as determined by the requirement of particular amino acid residues in the epitope, is shifted in these new antibody fragments. It was also evident that the VH/Vkappa pairing was not promiscuous, since antibody fragments selected by phage display retained light chain sequences very similar to the original hybridoma-derived light chain, proving that a high affinity interaction was very dependent on a co-operativity between both variable domains. These findings show that phage display technology might modify the binding properties of pre-existing, high affinity antibodies.}}, author = {{Ohlin, Mats and Owman, Henrik and Mach, Michael and Borrebaeck, Carl}}, issn = {{1872-9142}}, keywords = {{cytomegalovirus; human monoclonal antibody; glycoprotein B (gB); phage-display technology; antibody specificity}}, language = {{eng}}, number = {{1}}, pages = {{47--56}}, publisher = {{Pergamon Press Ltd.}}, series = {{Molecular Immunology}}, title = {{Light chain shuffling of a high affinity antibody results in a drift in epitope recognition}}, url = {{http://dx.doi.org/10.1016/0161-5890(95)00123-9}}, doi = {{10.1016/0161-5890(95)00123-9}}, volume = {{33}}, year = {{1996}}, }