Cross-linking reconsidered: binding and cross-linking fields and the cellular response.
We analyze a model for the reversible cross-linking of cell surface receptors by a collection of bivalent ligands with different affinities for the receptor as would be found in a polyclonal anti-receptor serum. We assume that the amount of cross-linking determines, via a monotonic function, the rate at which cells become activated and divide. In addition to the density of receptors on the cell surface, two quantities, the binding field and the cross-linking field, are needed to characterize the cross-linking curve, i.e., the equilibrium concentration of cross-linked receptors plotted as a function of the total ligand site concentration. The binding field is the sum of all ligand site concentrations weighted by their respective binding affinities, and the cross-linking field is the sum of all ligand site concentrations weighted by the product of their respective binding and cross-linking affinity and the total receptor density. Assuming that the cross-linking affinity decreases if the binding affinity decreases, we find that the height of the cross-linking curve decreases, its width narrows, and its center shifts to higher ligand site concentrations as the affinities decrease. Moreover, when we consider cross-linking-induced proliferation, we find that there is a minimum cross-linking affinity that must be surpassed before a clone can expand. We also show that under many circumstances a polyclonal antiserum would be more likely than a monoclonal antibody to lead to cross-linking-induced proliferation.
Sulzer
B
B
Los Alamos National Laboratory, New Mexico 87545, USA.
De Boer
R J
RJ
Perelson
A S
AS
D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D002455:Cell Division; D002999:Clone Cells; D003432:Cross-Linking Reagents; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D008024:Ligands; D011956:Receptors, Cell Surface