A response calculus for immobilized T cell receptor ligands.

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TitleA response calculus for immobilized T cell receptor ligands.
Publication TypeJournal Article
Year of Publication2001
AuthorsAndersen, PS, Menné, C, Mariuzza, RA, Geisler, C, Karjalainen, K
JournalJ Biol Chem
Volume276
Issue52
Pagination49125-32
Date Published2001 Dec 28
ISSN0021-9258
KeywordsAntibodies, Genes, Reporter, Ligands, Lymphocyte Activation, Mathematics, Models, Immunological, Protein Binding, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, Signal Transduction, Superantigens, T-Lymphocytes
Abstract

To address the molecular mechanism of T cell receptor (TCR) signaling, we have formulated a model for T cell activation, termed the 2D-affinity model, in which the density of TCR on the T cell surface, the density of ligand on the presenting surface, and their corresponding two-dimensional affinity determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated the importance of receptor cross-linking density in determining TCR signaling. Moreover, it was found that the functional two-dimensional affinity of TCR ligands was affected by the chemical composition of the ligand-presenting surface. This makes it possible that cell-bound TCR ligands, despite their low affinity in solution, are of optimal two-dimensional affinity thereby allowing effective TCR binding under physiological conditions, i.e. at low ligand densities in cellular interfaces.

DOI10.1074/jbc.M109396200
Alternate JournalJ. Biol. Chem.
PubMed ID11592972