A response calculus for immobilized T cell receptor ligands.
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.
Andersen
P S
PS
Institute for Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, Bldg. 24.2, Blegdamsvej 3C, Copenhagen DK-2200, Denmark. psa@symphogen.com
Menné
C
C
Mariuzza
R A
RA
Geisler
C
C
Karjalainen
K
K
D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D017930:Genes, Reporter; D008024:Ligands; D008213:Lymphocyte Activation; D008433:Mathematics; D018448:Models, Immunological; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018089:Superantigens / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D018089:Superantigens