B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production

Nat Immunol. 2001 Mar;2(3):269-74. doi: 10.1038/85339.


We describe here a newly identified member of the human B7 family, designated B7 homolog 3 (B7-H3), that shares 20-27% amino acid identity with other B7 family members. B7-H3 mRNA is not detectable in peripheral blood mononuclear cells, although it is found in various normal tissues and in several tumor cell lines. Expression of B7-H3 protein, however, can be induced on dendritic cells (DCs) and monocytes by inflammatory cytokines and a combination of phorbol myristate acetate (PMA) + ionomycin. Soluble B7-H3 protein binds a putative counter-receptor on activated T cells that is distinct from CD28, cytotoxic T lymphocyte antigen 4 (CTLA-4), inducible costimulator (ICOS) and PD-1. B7-H3 costimulates proliferation of both CD4+ and CD8+ T cells, enhances the induction of cytotoxic T cells and selectively stimulates interferon gamma (IFN-gamma) production in the presence of T cell receptor signaling. In contrast, inclusion of antisense B7-H3 oligonucleotides decreases the expression of B7-H3 on DCs and inhibits IFN-gamma production by DC-stimulated allogeneic T cells.Thus, we describe a newly identified costimulatory pathway that may participate in the regulation of cell-mediated immune responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD
  • B7 Antigens
  • B7-1 Antigen / genetics*
  • B7-1 Antigen / immunology*
  • B7-1 Antigen / metabolism
  • Cells, Cultured
  • Cloning, Molecular
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology
  • Humans
  • Interferon-gamma / biosynthesis*
  • Lymphocyte Activation*
  • Molecular Sequence Data
  • Protein Isoforms / genetics
  • Receptors, Immunologic / immunology
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • Antigens, CD
  • B7 Antigens
  • B7-1 Antigen
  • CD276 protein, human
  • Cytokines
  • Protein Isoforms
  • Receptors, Immunologic
  • Interferon-gamma

Associated data

  • GENBANK/AF302102