title: T-cell activation by soluble MHC oligomers can be described by a two-parameter binding model.
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 oligomers with different properties.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Stone
authors.forename: J R
authors.initials: JR
authors.lastname: Cochran
authors.forename: L J
authors.initials: LJ
authors.lastname: Stern
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D003432:Cross-Linking Reagents / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000502:physiology*; D008285:Major Histocompatibility Complex / Q000502:physiology*; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003432:Cross-Linking Reagents; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens