| Autor: |
Carayon P; Sanofi Recherche, Centre de Montpellier, France., Bord A, Gaillard JP, Vidal H, Gros P, Jansen FK |
| Jazyk: |
angličtina |
| Zdroj: |
Bioconjugate chemistry [Bioconjug Chem] 1993 Mar-Apr; Vol. 4 (2), pp. 146-52. |
| DOI: |
10.1021/bc00020a007 |
| Abstrakt: |
Anti-ricin-A-chain monoclonal antibodies (mAbs) were raised in order to study epitopes of the A-chain involved in the initiation of its transmembrane passage. Five nonoverlapping epitopes were selected by cluster formation using a cross-inhibition assay of mAbs from 172 specific hybridomas. For each cluster, representative high affinity mAbs were selected. These mAbs were disulfide-linked to F(ab')2 fragments of a mAb directed against the CD5 antigen. The cytotoxicity of ricin A-chain bound by affinity through different epitopes to these hybrid mAbs was explored on the CD5-positive CEM cells. Without any enhancer, the hybrids displayed cytotoxicity varying in IC50 within a range of 1-10; in the presence of the enhancer NH4Cl, this variation of activity was maintained ranging from 1 to 20; with the enhancer monensin, the variation of cytotoxicity of hybrids extended over a 1-80-fold range. These differences of cytotoxicity were not correlated with mAb properties such as the inhibition of A-chain enzymatic activity, the A-chain binding affinity, the capacity for releasing A-chain at low pH, or the capacity of hybrids for delivering A-chain on the cell surface. This lack of correlation strongly suggests that the different presentations of A-chain epitopes to the cell membrane may be the essential reason for cytotoxicity variations. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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