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


Journal of Clinical & Cellular Immunology

Author(s): Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB,

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Abstract 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. This article was published in Nat Immunol and referenced in Journal of Clinical & Cellular Immunology

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