Linked Life Data

7515151

Source:http://linkedlifedata.com/resource/pubmed/id/7515151

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1994-6-30
pubmed:abstractText
We have analysed the binding of variable domain-identical mouse monoclonal antibodies (mAb) of the IgG3, IgG1 and IgG2b subclasses, as well as F(ab')2 fragments derived from the IgG3 and IgG1 mAb, to a multivalent glycoprotein target. Using a biosensor device (BIAcore, Pharmacia Biosensor) that measures the mass of the antibody (or other receptor molecule) deposited on a sensor chip displaying the relevant epitopes, we found that the IgG3 mAb binds more effectively than the other antibody species at a high but not a low epitope density. The greater functional affinity associated with the IgG3 mAb, at high epitope density, was correlated with both slower dissociation rate constants and faster association rate constants in comparison with the IgG1 and IgG2b mAb and the F(ab')2 fragments derived from the IgG3 and IgG1 mAb. Evidence for slower dissociation kinetics for the IgG3 mAb versus the IgG1 and IgG2b mAb was also obtained by ELISA and flow cytometry. These results demonstrate that: (1) differences in heavy chain constant (CH) domains can significantly influence apparent functional affinity for multivalent antigen, as determined without the use of covalently modified primary or secondary antibodies; (2) differences in CH domains can alter both association and dissociation rate constants for interactions between IgG antibodies and multivalent antigen; and (3) these effects of CH domains depend on epitope density. The effect of constant region differences on the apparent association rate constants suggests new approaches for achieving better binding or functional effectiveness through antibody engineering.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
577-84
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Variable domain-identical antibodies exhibit IgG subclass-related differences in affinity and kinetic constants as determined by surface plasmon resonance.
pubmed:affiliation
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't