Characterization of a new human B7-related protein: B7RP-1 is the ligand to the co-stimulatory protein ICOS

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Abstract
Optimal T cell activation requires the interactions of co-stimulatory molecules, such as those in the CD28 and B7 protein families. Recently, we described the co-stimulatory properties of the murine ligand to ICOS, which we designated as B7RP-1. Here, we report the co-stimulation of human T cells through the human B7RP-1 and ICOS interaction. This ligand–receptor pair interacts with a KD ~ 33 nM and an off-rate with a t½ > 10 min. Interestingly, tumor necrosis factor (TNF)-α differentially regulates the expression of human B7RP-1 on B cells, monocytes and dendritic cells (DC). TNF-α enhances B7RP-1 expression on B cells and monocytes, while it inhibits it on DC. The human B7RP-1–Fc protein or cells that express membrane-bound B7RP-1 co-stimulate T cell proliferation in vitro. Specific cytokines, such as IFN-γ and IL-10, are induced by B7RP-1 co-stimulation. Although IL-2 levels are not significantly increased, B7RP-1 co-stimulation is dependent on IL-2. These experiments define the human ortholog to murine B7RP-1 and characterize its interaction with human ICOS.

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