B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production.
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.
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
A I
AI
Chapoval
J
J
Ni
J S
JS
Lau
R A
RA
Wilcox
D B
DB
Flies
D
D
Liu
H
H
Dong
G L
GL
Sica
G
G
Zhu
K
K
Tamada
L
L
Chen
D000595:Amino Acid Sequence; D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D011971:Receptors, Immunologic / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; C423237:CD276 protein, human; D016207:Cytokines; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D007371:Interferon-gamma