T-cell co-stimulation through B7RP-1 and ICOS.
Yoshinaga SK,
Whoriskey JS,
Khare SD,
Sarmiento U,
Guo J,
Horan T,
Shih G,
Zhang M,
Coccia MA,
Kohno T,
Tafuri-Bladt A,
Brankow D,
Campbell P,
Chang D,
Chiu L,
Dai T,
Duncan G,
Elliott GS,
Hui A,
McCabe SM,
Scully S,
Shahinian A,
Shaklee CL,
Van G,
Mak TW,
Senaldi G.
Amgen Inc., Thousand Oaks, California 91320, USA. syoshina@amgen.com
T-cell activation requires co-stimulation through receptors such as CD28 and antigen-specific signalling through the T-cell antigen receptor. Here we describe a new murine costimulatory receptor-ligand pair. The receptor, which is related to CD28 and is the homologue of the human protein ICOS, 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-I 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.
PMID: 10617205 [PubMed - indexed for MEDLINE]