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

Nature. 1999 Dec 16;402(6763):827-32. doi: 10.1038/45582.


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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism*
  • CHO Cells
  • COS Cells
  • Cells, Cultured
  • Cricetinae
  • DNA, Complementary
  • Dermatitis, Contact / immunology
  • Female
  • Gene Expression
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Ligands
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Protein Binding
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • Antigens, Differentiation, T-Lymphocyte
  • B7-1 Antigen
  • DNA, Complementary
  • ICOS protein, human
  • Icos protein, mouse
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Ligands
  • Recombinant Fusion Proteins