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Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells

A stochastic reaction–diffusion model was developed to describe the binding of labeled monoclonal antibodies (mAbs) to CD4 receptors on the surface of T cells. The mAbs diffused to, adsorbed on, and underwent monovalent and bivalent binding to CD4 receptors on the cell surface. The model predicted t...

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Autores principales: Wang, Lili, DeRose, Paul C., Inwood, Sarah L., Gaigalas, Adolfas K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504294/
https://www.ncbi.nlm.nih.gov/pubmed/32846978
http://dx.doi.org/10.3390/ijms21176086
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author Wang, Lili
DeRose, Paul C.
Inwood, Sarah L.
Gaigalas, Adolfas K.
author_facet Wang, Lili
DeRose, Paul C.
Inwood, Sarah L.
Gaigalas, Adolfas K.
author_sort Wang, Lili
collection PubMed
description A stochastic reaction–diffusion model was developed to describe the binding of labeled monoclonal antibodies (mAbs) to CD4 receptors on the surface of T cells. The mAbs diffused to, adsorbed on, and underwent monovalent and bivalent binding to CD4 receptors on the cell surface. The model predicted 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 monovalently and bivalently bound mAbs. The predicted coefficient of variation (CV%) of the (ABC) values translated directly to a corresponding CV% of the measured mean fluorescence intensity (MFI). The predicted CV% was about 0.2% from the intrinsic fluctuations of the stochastic reaction process, about 5% after inclusion of the known fluctuations in the number of available CD4 receptors, and about 11% when fluctuations in bivalent binding affinity were included. The fluorescence detection process is expected to contribute approximately 7%. The abovementioned contributions to CV% sum up to approximately 13%. Work is underway to reconcile the predicted values and the measured values of 17% to 22%.
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spelling pubmed-75042942020-09-24 Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells Wang, Lili DeRose, Paul C. Inwood, Sarah L. Gaigalas, Adolfas K. Int J Mol Sci Article A stochastic reaction–diffusion model was developed to describe the binding of labeled monoclonal antibodies (mAbs) to CD4 receptors on the surface of T cells. The mAbs diffused to, adsorbed on, and underwent monovalent and bivalent binding to CD4 receptors on the cell surface. The model predicted 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 monovalently and bivalently bound mAbs. The predicted coefficient of variation (CV%) of the (ABC) values translated directly to a corresponding CV% of the measured mean fluorescence intensity (MFI). The predicted CV% was about 0.2% from the intrinsic fluctuations of the stochastic reaction process, about 5% after inclusion of the known fluctuations in the number of available CD4 receptors, and about 11% when fluctuations in bivalent binding affinity were included. The fluorescence detection process is expected to contribute approximately 7%. The abovementioned contributions to CV% sum up to approximately 13%. Work is underway to reconcile the predicted values and the measured values of 17% to 22%. MDPI 2020-08-24 /pmc/articles/PMC7504294/ /pubmed/32846978 http://dx.doi.org/10.3390/ijms21176086 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Lili
DeRose, Paul C.
Inwood, Sarah L.
Gaigalas, Adolfas K.
Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells
title Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells
title_full Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells
title_fullStr Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells
title_full_unstemmed Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells
title_short Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells
title_sort stochastic reaction–diffusion model of the binding of monoclonal antibodies to cd4 receptors on the surface of t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504294/
https://www.ncbi.nlm.nih.gov/pubmed/32846978
http://dx.doi.org/10.3390/ijms21176086
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