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International Immunology, Vol. 12, No. 10, 1439-1447, October 2000
© 2000 Japanese Society for Immunology

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

Steven K. Yoshinaga, Ming Zhang, Jeanne Pistillo1, Tom Horan, Sanjay D. Khare1, Kent Miner1, Michael Sonnenberg, Tom Boone2, David Brankow, Tianang Dai, John Delaney2, Hong Han, Ariela Hui, Tadahiko Kohno, Raffi Manoukian, John S. Whoriskey and Marco A. Coccia1

Exploratory Research,
1 Pharmacology and
2 Process Development, Amgen Inc., Thousand Oaks, CA 91320, USA

Correspondence to: S. K. Yoshinaga

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 t1/2 > 10 min. Interestingly, tumor necrosis factor (TNF)-{alpha} differentially regulates the expression of human B7RP-1 on B cells, monocytes and dendritic cells (DC). TNF-{alpha} 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-{gamma} 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.

Keywords: antigen-presenting cells, dendritic cells, cytokines, co-stimulation, TCR

Transmitting editor: T. Hünig


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