T-cell co-stimulation through B7RP-1 and ICOS

Steven K. Yoshinaga (), John S. Whoriskey, Sanjay D. Khare, Ulla Sarmiento, Jane Guo, Tom Horan, Grace Shih, Ming Zhang, Marco A. Coccia, Tadahiko Kohno, Anna Tafuri-Bladt, David Brankow, Pauline Campbell, David Chang, Laura Chiu, Tianang Dai, Gordon Duncan, Gary S. Elliott, Ariela Hui, Susan M. McCabe, Sheila Scully, Arda Shahinian, Christine L. Shaklee, Gwyneth Van, Tak W. Mak and Giorgio Senaldi
Additional contact information
Steven K. Yoshinaga: Amgen Inc.
John S. Whoriskey: Amgen Inc.
Sanjay D. Khare: Amgen Inc.
Ulla Sarmiento: Amgen Inc.
Jane Guo: Amgen Inc.
Tom Horan: Amgen Inc.
Grace Shih: Amgen Inc.
Ming Zhang: Amgen Inc.
Marco A. Coccia: Amgen Inc.
Tadahiko Kohno: Amgen Inc.
Anna Tafuri-Bladt: Amgen Research Institute
David Brankow: Amgen Inc.
Pauline Campbell: Amgen Inc.
David Chang: Amgen Inc.
Laura Chiu: Amgen Inc.
Tianang Dai: Amgen Inc.
Gordon Duncan: Amgen Research Institute
Gary S. Elliott: Amgen Inc.
Ariela Hui: Amgen Inc.
Susan M. McCabe: Amgen Inc.
Sheila Scully: Amgen Inc.
Arda Shahinian: Amgen Research Institute
Christine L. Shaklee: Amgen Inc.
Gwyneth Van: Amgen Inc.
Tak W. Mak: Amgen Research Institute
Giorgio Senaldi: Amgen Inc.

Nature, 1999, vol. 402, issue 6763, 827-832

Abstract: Abstract T-cell activation requires co-stimulation through receptors such as CD28 (refs 1,2,3) and antigen-specific signalling through the T-cell antigen receptor. Here we describe a new murine co-stimulatory receptor–ligand pair. The receptor, which is related to CD28 and is the homologue of the human protein ICOS4, is expressed on activated T cells and resting memory T cells. The ligand, which has homology to B7 molecules and is called B7-related protein-1 (B7RP-1), is expressed on B cells and macrophages. ICOS and B7RP-1 do not interact with proteins in the CD28–B7 pathway, and B7RP-1 co-stimulates T cells in vitro independently of CD28. Transgenic mice expressing a B7RP-1–Fc fusion protein show lymphoid hyperplasia in the spleen, lymph nodes and Peyer's patches. Presensitized mice treated with B7RP-1–Fc during antigen challenge show enhanced hypersensitivity. Therefore, B7RP-1 exhibits co-stimulatory activities in vitro and in vivo. ICOS and B7RP-1 define a new and distinct receptor–ligand pair that is structurally related to CD28–B7 and is involved in the adaptive immune response.

Date: 1999
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DOI: 10.1038/45582

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