Back to Search
Start Over
Enhanced antigen-antibody binding affinity mediated by an anti-idiotypic antibody
- Source :
- Biochemistry. 26:5275-5282
- Publication Year :
- 1987
- Publisher :
- American Chemical Society (ACS), 1987.
-
Abstract
- The authors previously described the production of four monoclonal antibodies to the ..beta..-adrenergic receptor antagonist alprenolol. One of these antibodies, 5B7 (IgG/sub 2a/, kappa), was used to raise anti-idiotypic antisera in rabbits. In contrast to the expected results, one of the anti-idiotypic antisera (R9) promotes (/sup 125/I)iodocyanopinodolol (ICYP) binding to antibody 5B7. In the presence of R9, the dissociation constant decreases 100-fold from 20 to 0.3 nM. This increase in binding affinity of antibody 5B7 for ICYP is not observed in the presence of preimmune, rabbit anti-mouse or anti-idiotypic antisera generated to a monoclonal antibody of a different specificity. Furthermore, R9 in the absence of 5B7 does not bind ICYP. The F(ab) fragments of 5B7 and T9 behaved in a similar manner, and the soluble complex responsible for the high-affinity interaction with ICYP can be identified by gel filtration chromatography. The elution position of the complex is consistent with a 5B7 F(ab)-R9 F(ab) dimer, indicating that polyvalency is not responsible for the enhanced ligand binding. Kinetic analysis of ICYP-5B7 binding revealed that the rate of ICYP dissociation from 5B7 in the presence of R9 is approximately 100 times slower than in the absence of R9, consistent with the 100-fold changemore » in binding affinity of 5B7 for ICYP. The available data best fit a model in which an anti-idiotypic antibody binds at or near the binding site of the idiotype participating in the formation of a hybrid ligand binding site. This would allow increased contact of the ligand with the idiotype-anti-idiotype complex and result in an enhanced affinity of the ligand interaction.« less
- Subjects :
- Idiotype
medicine.drug_class
Antigen-Antibody Complex
Monoclonal antibody
Biochemistry
Immunoglobulin Fab Fragments
Immunoglobulin Idiotypes
medicine
Animals
Iodocyanopindolol
Binding site
Alprenolol
Antiserum
biology
Chemistry
Antibodies, Monoclonal
Ligand (biochemistry)
Receptor antagonist
Molecular biology
Dissociation constant
Kinetics
Immunoglobulin G
Pindolol
biology.protein
Thermodynamics
Rabbits
Antibody
Subjects
Details
- ISSN :
- 15204995 and 00062960
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Biochemistry
- Accession number :
- edsair.doi.dedup.....6fa4b4da96d6ce437d7cafc1c946a297