Stochastic diffusion-reaction model of the binding of monoclonal antibodies to CD4 receptors on the surface of T cells

Published

August 24, 2020

Author(s)

Paul DeRose, Sarah L. Inwood, Adolfas K. Gaigalas, Lili Wang

Abstract

A stochastic diffusion-reaction model was developed to describe the labeling process in which labeled monoclonal antibodies (mAb) were bound to CD4 receptors on the surface of T cells. The mass transport of mAb to the surface of the cell was described by a diffusive process between a group of three layers surrounding the cell. The outermost layer, called the transition layer, was in contact with the bulk suspension and was the starting point for the mass transfer. The boundary layer was in contact with the transition layer as well as the innermost layer, called cell layer, which was in contact with the surface of the cell. The mAb adsorbed on the cell surface and underwent monovalent and bivalent binding to CD4 receptors on the cell surface. The model gave the time dependent nature of all populations involved in the labeling process. At large time, the populations reached equilibrium values giving the number of antibodies bound to the T cell (ABC) defined as the sum of the monovalently and bivalently bound mAb. The (ABC) value was directly related to the mean fluorescence intensity (MFI) of the cell as measured by the flow cytometer. The predicted CV% of the (ABC) values translated directly to a corresponding CV% of the measured (MFI) signal. The predicted CV% of the number of (ABC) is about 0.2% from the intrinsic fluctuations of the stochastic reaction process, and about 5% from the known fluctuations in the number of available CD4 receptors on T cells. Including fluctuations in the bivalent binding affinity increased the CV% of (ABC) to 11%. The fluorescence detection process is expected to contribute about 7% to the measured CV%. The above-mentioned contributions to CV% add up to about 13% which is smaller than the measured values of 17% and 22%. It is expected that a careful attention to all possible fluctuations in T cell properties such as receptor number and binding constants will reconcile the predicted CV% with the observed values.

Citation

International Journal of Molecular Sciences

Pub Type

Journals

Keywords

stochastic simulation, CD4+ T cell, labeling reaction, CV%, monovalent, bivalent

Citation

DeRose, P. , Inwood, S. , Gaigalas, A. and Wang, L. (2020), Stochastic diffusion-reaction model of the binding of monoclonal antibodies to CD4 receptors on the surface of T cells, International Journal of Molecular Sciences (Accessed April 19, 2025)