A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies

TL;DR

This paper develops an equilibrium biophysical model to understand cell adhesion mediated by antibodies and drugs, comparing it with experimental data to reveal the importance of epitope immobility in adhesion mechanisms.

Contribution

It introduces a novel model incorporating epitope heterogeneity and immobility, providing insights into antibody-mediated cell adhesion mechanisms.

Findings

Immobile epitopes are more consistent with experimental data.

A model with fully mobile epitopes does not fit the data.

Parameter space for binding is quantitatively described.

Abstract

A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data. We also quantitatively describe the parameter space in which binding occurs. Our results point toward mechanisms relating epitope immobility to cell adhesion and offer insight into the activity of an important class of drugs.