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Biophys J, November 2001, p. 2547-2557, Vol. 81, No. 5

T-Cell Activation by Soluble MHC Oligomers Can Be Described by a Two-Parameter Binding Model

Jennifer D. Stone, Jennifer R. Cochran, and Lawrence J. Stern

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA

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.

Biophys J, November 2001, p. 2547-2557, Vol. 81, No. 5
© 2001 by the Biophysical Society   0006-3495/01/11/2547/11  $2.00


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