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,
*
The Ben May Institute for Cancer Research, Departments of
Medicine and
Pathology, and Committee on Immunology, University of Chicago, Chicago, IL 60637; and Departments of
Oncology and
¶ Pathology, Johns Hopkins University, Baltimore, MD 21218
Ag-specific immune tolerance in clinical organ transplantation is
currently an unrealized but critical goal of transplant biology. The
specificity and avidity of multimerized MHC-peptide complexes suggests
their potential ability to modulate T cell sensitization and effector
functions. In this study, we examined the ability of MHC-peptide dimers
to modulate T cell function both in vitro and in vivo. Soluble MHC
dimers induced modulation of surface TCR expression and inhibited T
cell cytolytic activity at nanomolar concentrations in vitro.
Furthermore, engagement of TCR by soluble dimers resulted in
phosphorylation of the TCR 
-chain and recruitment and
phosphorylation of -associated protein-70 to the signaling complex,
the latter of which increased upon dimer cross-linking. Significantly,
Ag-specific inhibition of an alloreactive TCR-transgenic T cell
population in vivo resulted in consequent outgrowth of an allogeneic
tumor. The prolonged Ag-specific suppression of expansion and/or
effector function of cognate T cells in vivo suggests that soluble MHC
dimers may be a means of inducing sustained Ag-specific T cell
unresponsiveness in vivo.
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