Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies
| العنوان: | Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies |
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| المؤلفون: | Michael N. Margolies, David R. Parks, Lisa L. Peterson, Leonard A. Herzenberg, Meredith Mudgett-Hunter, David J. Panka, Edgar Haber |
| المصدر: | Proceedings of the National Academy of Sciences. 85:3080-3084 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 1988. |
| سنة النشر: | 1988 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.85.9.3080 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b9d93134277a1dadfddbf4e605f922e https://doi.org/10.1073/pnas.85.9.3080 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1b9d93134277a1dadfddbf4e605f922e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.85.9.3080 |