title: T-cell co-stimulation through B7RP-1 and ICOS.
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.
authors.affiliation: Amgen Inc., Thousand Oaks, California 91320, USA. syoshina@amgen.com
authors.forename: S K
authors.initials: SK
authors.lastname: Yoshinaga
authors.forename: J S
authors.initials: JS
authors.lastname: Whoriskey
authors.forename: S D
authors.initials: SD
authors.lastname: Khare
authors.forename: U
authors.initials: U
authors.lastname: Sarmiento
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: T
authors.initials: T
authors.lastname: Horan
authors.forename: G
authors.initials: G
authors.lastname: Shih
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: M A
authors.initials: MA
authors.lastname: Coccia
authors.forename: T
authors.initials: T
authors.lastname: Kohno
authors.forename: A
authors.initials: A
authors.lastname: Tafuri-Bladt
authors.forename: D
authors.initials: D
authors.lastname: Brankow
authors.forename: P
authors.initials: P
authors.lastname: Campbell
authors.forename: D
authors.initials: D
authors.lastname: Chang
authors.forename: L
authors.initials: L
authors.lastname: Chiu
authors.forename: T
authors.initials: T
authors.lastname: Dai
authors.forename: G
authors.initials: G
authors.lastname: Duncan
authors.forename: G S
authors.initials: GS
authors.lastname: Elliott
authors.forename: A
authors.initials: A
authors.lastname: Hui
authors.forename: S M
authors.initials: SM
authors.lastname: McCabe
authors.forename: S
authors.initials: S
authors.lastname: Scully
authors.forename: A
authors.initials: A
authors.lastname: Shahinian
authors.forename: C L
authors.initials: CL
authors.lastname: Shaklee
authors.forename: G
authors.initials: G
authors.lastname: Van
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.forename: G
authors.initials: G
authors.lastname: Senaldi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D019556:COS Cells; D002478:Cells, Cultured; D006224:Cricetinae; D018076:DNA, Complementary; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018076:DNA, Complementary; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands; D011993:Recombinant Fusion Proteins