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J. Biol. Chem., Vol. 276, Issue 36, 33452-33457, September 7, 2001
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From the Similar to native peptide/MHC ligands, bacterial
superantigens have been found to bind with low affinity to the T
cell receptor (TCR). It has been hypothesized that low ligand affinity
is required to allow optimal TCR signaling. To test this, we generated
variants of Staphylococcus enterotoxin C3 (SEC3) with up to
a 150-fold increase in TCR affinity. By stimulating T cells with SEC3
molecules immobilized onto plastic surfaces, we demonstrate that
increasing the affinity of the SEC3/TCR interaction caused a
proportional increase in the ability of SEC3 to activate T cells. Thus,
the potency of the SEC3 variants correlated with enhanced binding without any optimum in the binding range covered by native TCR ligands.
Comparable studies using anti-TCR antibodies of known affinity
confirmed these observations. By comparing the biological potency of the two sets of ligands, we found a significant correlation between ligand affinity and ligand potency indicating that it is the
density of receptor-ligand complexes in the T cell contact area that
determines TCR signaling strength.
Role of the T Cell Receptor Ligand Affinity in T Cell Activation
by Bacterial Superantigens*
§,,,
Institute for Medical Microbiology and
Immunology, University of Copenhagen, Blegdamsvej 3C, DK-2200
Copenhagen, 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
*
This research was supported 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 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.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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