| T-cell activation by soluble MHC oligomers can be described by a two-parameter binding model. | |
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MedLine Citation:
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PMID: 11606269 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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T-cell activation is essential for initiation and control of immune system function. T cells are activated by interaction of cell-surface antigen receptors with major histocompatibility complex (MHC) proteins on the surface of other cells. Studies using soluble oligomers of MHC-peptide complexes and other types of receptor cross-linking agents have supported an activation mechanism that involves T cell receptor clustering. Receptor clustering induced by incubation of T cells with MHC-peptide oligomers leads to the induction of T-cell activation processes, including downregulation of engaged receptors and upregulation of the cell-surface proteins CD69 and CD25. Dose-response curves for these T-cell activation markers are bell-shaped, with different maxima and midpoints, depending on the valency of the soluble oligomer used. In this study, we have analyzed the activation behavior using a mathematical model that describes the binding of multivalent ligands to cell-surface receptors. We show that a simple equilibrium binding model accurately describes the activation data for CD4(+) T cells treated with MHC-peptide oligomers of varying valency. The model can be used to predict activation and binding behavior for T cells and MHC oligomers with different properties. |
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Authors:
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J D Stone; J R Cochran; L J Stern |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Biophysical journal Volume: 81 ISSN: 0006-3495 ISO Abbreviation: Biophys. J. Publication Date: 2001 Nov |
Date Detail:
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Created Date: 2001-10-18 Completed Date: 2002-02-19 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370626 Medline TA: Biophys J Country: United States |
Other Details:
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Languages: eng Pagination: 2547-57 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD
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metabolism Antigens, Differentiation, T-Lymphocyte / metabolism Binding Sites / physiology Binding, Competitive / physiology Cross-Linking Reagents / metabolism* Dose-Response Relationship, Immunologic Down-Regulation / physiology Humans Lymphocyte Activation / physiology* Major Histocompatibility Complex / physiology* Models, Biological* Receptors, Antigen, T-Cell / metabolism* Receptors, Interleukin-2 / metabolism T-Lymphocytes / cytology, metabolism* Up-Regulation / physiology |
| Grant Support | |
ID/Acronym/Agency:
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N01-AI48833/AI/NIAID NIH HHS; T32-GM08334/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Antigens, Differentiation, T-Lymphocyte; 0/CD69 antigen; 0/Cross-Linking Reagents; 0/Receptors, Antigen, T-Cell; 0/Receptors, Interleukin-2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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