T-cell activation by soluble MHC oligomers can be described by a two-parameter binding model

Biophysical Journal
J D StoneL J Stern

Abstract

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 olig...Continue Reading

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Citations

Nov 12, 2009·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Joseph J SabatinoBrian D Evavold
Sep 6, 2002·Journal of Immunological Methods·Thomas O CameronLawrence J Stern
May 26, 2012·Langmuir : the ACS Journal of Surfaces and Colloids·Jennifer L TangTodd Sulchek
Mar 13, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Erin R Steenblock, Tarek M Fahmy
Apr 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Shi ZhongMichelle Krogsgaard
Apr 30, 2003·The Journal of General Physiology·Tatyana I RokitskayaYuri N Antonenko
Jun 30, 2012·Journal of the Royal Society, Interface·James CurrieCarmen Molina-París
Dec 20, 2011·IEEE Transactions on Nanobioscience·Nicole M Moore, Shelly E Sakiyama-Elbert
Sep 10, 2014·Biochimica Et Biophysica Acta·Karlo PericaJonathan P Schneck
May 13, 2014·Frontiers in Immunology·Mario CastroCarmen Molina-París
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Oct 22, 2002·American Journal of Physiology. Cell Physiology·Carme PelegríMargarida Castell
Jun 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam S ChervinDavid M Kranz
Jun 14, 2014·Advanced Healthcare Materials·Rebecca R PompanoAnita S Chong
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer D Stone, Lawrence J Stern
Dec 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Valérie I Mallet-DesigneLuc Teyton
Oct 31, 2020·International Journal of Molecular Sciences·Elizabeth M KolawoleBrian D Evavold
Jul 14, 2021·Journal for Immunotherapy of Cancer·Mathilde PoussinStephen Demarest
Aug 14, 2021·The Journal of Biological Chemistry·Athéna C Patterson-OrazemRaquel L Lieberman

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