Lectin-dependent modulation of interaction between human alpha-fetoprotein and its monoclonal antibodies. Epitope mapping.
The effect of lentil lectin (LCA) on the binding of mouse monoclonal antibody (MoAb) against human alpha-fetoprotein (AFP) to LCA-nonreactive AFP-L1 and LCA-reactive AFP-L3 was studied on a panel of 30 MoAbs provided by the TD-2 Workshop of ISOBM for epitope mapping. LCA inhibited the binding of MoAbs 93 and 98 to AFP-L3 but not to AFP-L1, indicating that there was a competition between the MoAbs and LCA for the AFP sugar chain. With MoAbs 100, 109, 118, and 120, LCA rather increased the binding to AFP-L3 over that to AFP-L1. These modulating effects of LCA on the MoAb binding to AFP-L3 were abolished by periodate treatment of the AFP preparations without affecting the binding of MoAb to AFP. Concanavalin A had similar inhibiting and enhancing effects on MoAb binding, but equally to AFP-L1 and AFP-L3, both of which are fully reactive with concanavalin A. The results suggested that MoAbs 93 and 98 recognized epitopes closely related to sugar chain, and their binding to AFP-L3 was inhibited by the bound LCA due to steric hindrance. The enhanced binding of some MoAbs to AFP-L3 over AFP-L1 with LCA, or both glycoforms of AFP with concanavalin A, may be explained by postulating an allosteric mechanism mediated by the oligosaccharide-lectin interaction.
Department of Public Health, Okayama University Medical School, Japan. ktaketa@med.okayama-u.ac.jp
K
K
Taketa
K
K
Kamakura
S
S
Satomura
H
H
Taga
D000818:Animals; D000911:Antibodies, Monoclonal / Q000187:drug effects* / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D018604:Epitope Mapping; D006023:Glycoproteins / Q000187:drug effects / Q000276:immunology; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D051379:Mice; D037121:Plant Lectins; D011487:Protein Conformation; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D037102:Lectins; D037121:Plant Lectins; D000509:alpha-Fetoproteins; C033619:lentil lectin; D003208:Concanavalin A