The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell Repertoire

The immune system maintains a highly diverse T-cell repertoire,which is shaped by active interactions between developing thymocytesand endogenous peptide/MHC molecules through the principle ofpositive and negative selections. Detours et al. developed aquantitative model addressing key immunologic no...

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Main Author: Guanyu Wang
Format: Article
Language:English
Published: AIMS Press 2004-10-01
Series:Mathematical Biosciences and Engineering
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Online Access:https://www.aimspress.com/article/doi/10.3934/mbe.2005.2.153
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author Guanyu Wang
author_facet Guanyu Wang
author_sort Guanyu Wang
collection DOAJ
description The immune system maintains a highly diverse T-cell repertoire,which is shaped by active interactions between developing thymocytesand endogenous peptide/MHC molecules through the principle ofpositive and negative selections. Detours et al. developed aquantitative model addressing key immunologic notions such asselection, alloreactivity, and self-restriction. The model was basedon the assumption that the clone size is uniformly distributed inthe naive T-cell repertoire. However, recent biological findingshave indicated that the naive T-cell repertoire is highly skewed,due to the uneven proliferation of premigrant single-positivethymocytes. In this paper, the model is revised to include these newfindings. The effects of the uneven clonal expansion are investigated in detailand their biological significance is discussed. It is found that theuneven clonal expansion can significantly enhance the self-MHCrestriction, while avoiding decreasing the alloreactivity. The clonal expansiontherefore appears to be an additional selection event, resulting infine tuning of the repertoire. In this way, T-cells reaching theperiphery pool can fulfill maximum competence: both highself-restriction and high alloreactivity.
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spelling doaj-art-fb81229457114751bc9b873e81d67b032025-01-24T01:47:55ZengAIMS PressMathematical Biosciences and Engineering1551-00182004-10-012115316810.3934/mbe.2005.2.153The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell RepertoireGuanyu Wang0Department of Pathology and laboratory Medicine, The University of Texas Medical School at Houston, Houston, TX 77030The immune system maintains a highly diverse T-cell repertoire,which is shaped by active interactions between developing thymocytesand endogenous peptide/MHC molecules through the principle ofpositive and negative selections. Detours et al. developed aquantitative model addressing key immunologic notions such asselection, alloreactivity, and self-restriction. The model was basedon the assumption that the clone size is uniformly distributed inthe naive T-cell repertoire. However, recent biological findingshave indicated that the naive T-cell repertoire is highly skewed,due to the uneven proliferation of premigrant single-positivethymocytes. In this paper, the model is revised to include these newfindings. The effects of the uneven clonal expansion are investigated in detailand their biological significance is discussed. It is found that theuneven clonal expansion can significantly enhance the self-MHCrestriction, while avoiding decreasing the alloreactivity. The clonal expansiontherefore appears to be an additional selection event, resulting infine tuning of the repertoire. In this way, T-cells reaching theperiphery pool can fulfill maximum competence: both highself-restriction and high alloreactivity.https://www.aimspress.com/article/doi/10.3934/mbe.2005.2.153mathematical modelingprobability theorypositive/negative selectionclonal expansiont-cell development.
spellingShingle Guanyu Wang
The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell Repertoire
Mathematical Biosciences and Engineering
mathematical modeling
probability theory
positive/negative selection
clonal expansion
t-cell development.
title The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell Repertoire
title_full The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell Repertoire
title_fullStr The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell Repertoire
title_full_unstemmed The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell Repertoire
title_short The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell Repertoire
title_sort effects of affinity mediated clonal expansion of premigrant thymocytes on the periphery t cell repertoire
topic mathematical modeling
probability theory
positive/negative selection
clonal expansion
t-cell development.
url https://www.aimspress.com/article/doi/10.3934/mbe.2005.2.153
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