T-cell co-stimulation through B7RP-1 and ICOS - PubMed (original) (raw)

. 1999 Dec 16;402(6763):827-32.

doi: 10.1038/45582.

J S Whoriskey, S D Khare, U Sarmiento, J Guo, T Horan, G Shih, M Zhang, M A Coccia, T Kohno, A Tafuri-Bladt, D Brankow, P Campbell, D Chang, L Chiu, T Dai, G Duncan, G S Elliott, A Hui, S M McCabe, S Scully, A Shahinian, C L Shaklee, G Van, T W Mak, G Senaldi

Affiliations

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

S K Yoshinaga et al. Nature. 1999.

Abstract

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.

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