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Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104
Activation of T cells is dependent upon coordinate engagement of Ag
and costimulator receptors on their surfaces. In the case of the Ag
receptors (TCRs), activation thresholds have been defined, with the
number of TCRs that must be triggered to stimulate cytokine secretion
by individual activated T cells differing for the various cytokines. In
the present study, we have determined whether comparable activation
thresholds exist for the costimulator receptors on T cells. To
facilitate this type of quantitative costimulator analysis, we
developed a novel two-step protein transfer approach that permits
delivery of graded amounts of proteins to APC surfaces. By adding a
human B7-1 · Fc
1 (Fc domain of human IgG1) fusion
protein to cells precoated with palmitated protein A, fine titration of
the B7-1 extracellular domain was achieved. The
B7-1 · Fc1 reincorporated into cell membranes by
this method retained costimulator function, as measured by an in vitro
proliferation assay. The degree of proliferation was dependent on the
surface density of B7-1 · Fc1. Significantly, the
threshold B7-1 · Fc1 density required for cytokine
production differed between IFN- and IL-2 and mirrored the hierarchy
(IFN- < IL-2) described previously for the TCR activation
threshold. Hence, this study invokes a novel protein transfer strategy
to establish that the levels of surface costimulator on APCs can
dictate both the magnitude and the quality of evoked T cell responses.
The notion of costimulator receptor activation thresholds
emerges.
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