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Originally published In Press as doi:10.1074/jbc.M109396200 on October 9, 2001
J. Biol. Chem., Vol. 276, Issue 52, 49125-49132, December 28, 2001
A Response Calculus for Immobilized T Cell Receptor
Ligands*
Peter S.
Andersen §,
Charlotte
Menné,
Roy A.
Mariuzza¶,
Carsten
Geisler, and
Klaus
Karjalainen
From the Institute for Medical Microbiology and
Immunology, University of Copenhagen, The Panum Institute, Bldg. 24.2, Blegdamsvej 3C, Copenhagen DK-2200, Denmark, the ¶ Center for
Advanced Research in Biotechnology, University of Maryland, Rockville,
Maryland 20850, and the Basel Institute of Immunology,
Grenzsacherstrasse 487, postfach CH-4005, Basel,
Switzerland
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.
*
This research was supported in part by the Danish Medical
Research Council (to C. G. and S. B), the Danish Cancer Society (to
C. G.), and the National Institutes of Health (to R. A. M.). The
Basel Institute for Immunology was founded and is supported by
Hoffmann-LaRoche Ltd., Basel, Switzerland.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§
Supported by fellowships from the Danish Natural Science Research
council and the Danish Medical Research Council. To whom correspondence
should be addressed: Symphogen A/S, Elektrovej, Bldg. 375, Lyngby
DK-2800, Denmark. Tel.: 45-45-26-50-69; Fax: 45-45-26-50-60;
E-mail: psa@symphogen.com.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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