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

Biophys J. 2001 Nov;81(5):2547-57. doi: 10.1016/S0006-3495(01)75899-7.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Binding Sites / physiology
  • Binding, Competitive / physiology
  • Cross-Linking Reagents / metabolism*
  • Dose-Response Relationship, Immunologic
  • Down-Regulation / physiology
  • Humans
  • Lectins, C-Type
  • Lymphocyte Activation / physiology*
  • Major Histocompatibility Complex / physiology*
  • Models, Biological*
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Interleukin-2 / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Up-Regulation / physiology


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Cross-Linking Reagents
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2