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Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies
- Source :
- Proceedings of the National Academy of Sciences. 85:3080-3084
- Publication Year :
- 1988
- Publisher :
- Proceedings of the National Academy of Sciences, 1988.
-
Abstract
- Rare spontaneous variants of the anti-digoxin antibody-producing hybridoma 40-150 (Ko = 5.4 x 10(9) M-1) were selected for altered antigen binding by two-color fluorescence-activated cell sorting. The parent antibody binds digoxin 890-fold greater than digitoxin. The variant 40-150 A2.4 has reduced affinity for digoxin (Ko = 9.2 x 10(6) M-1) and binds digoxin 33-fold greater than digitoxin. A second-order variant, derived from 40-150 A2.4 (designated 40-150 A2.4 P.10), demonstrated partial regain of digoxin binding (Ko = 4.4 x 10(8) M-1). The altered binding of the variant 40-150 A2.4 was accounted for by a point mutation resulting in substitution of arginine for serine at position 94 in the heavy chain variable region. Antibody 40-150 A2.4 P.10 also contains this arginine but owes its enhanced antigen binding to deletion of two amino acids from the heavy chain amino terminus. This unusual sequence alteration in an immunoglobulin framework region confers increased affinity for antigen.
- Subjects :
- Digoxin
Arginine
Mice, Inbred A
medicine.drug_class
Digitoxin
Molecular Sequence Data
Biology
Monoclonal antibody
Antibodies
Cell Line
Serine
Mice
Antigen
medicine
Animals
Amino Acid Sequence
Framework region
chemistry.chemical_classification
Multidisciplinary
Base Sequence
Flow Cytometry
Antigenic Variation
Molecular biology
Amino acid
chemistry
Biochemistry
Mutation
biology.protein
Antibody
Research Article
medicine.drug
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 85
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....1b9d93134277a1dadfddbf4e605f922e