Characterization of a new human B7-related protein: B7RP-1 is the ligand to the co-stimulatory protein ICOS.
Optimal T cell activation requires the interactions of co-stimulatory molecules, such as those in the CD28 and B7 protein families. Recently, we described the co-stimulatory properties of the murine ligand to ICOS, which we designated as B7RP-1. Here, we report the co-stimulation of human T cells through the human B7RP-1 and ICOS interaction. This ligand-receptor pair interacts with a K:(D) approximately 33 nM and an off-rate with a t((1/2)) > 10 min. Interestingly, tumor necrosis factor (TNF)-alpha differentially regulates the expression of human B7RP-1 on B cells, monocytes and dendritic cells (DC). TNF-alpha enhances B7RP-1 expression on B cells and monocytes, while it inhibits it on DC. The human B7RP-1-Fc protein or cells that express membrane-bound B7RP-1 co-stimulate T cell proliferation in vitro. Specific cytokines, such as IFN-gamma and IL-10, are induced by B7RP-1 co-stimulation. Although IL-2 levels are not significantly increased, B7RP-1 co-stimulation is dependent on IL-2. These experiments define the human ortholog to murine B7RP-1 and characterize its interaction with human ICOS.
Yoshinaga
S K
SK
Exploratory Research, Pharmacology and Process Development, Amgen Inc., Thousand Oaks, CA 91320, USA.
Zhang
M
M
Pistillo
J
J
Horan
T
T
Khare
S D
SD
Miner
K
K
Sonnenberg
M
M
Boone
T
T
Brankow
D
D
Dai
T
T
Delaney
J
J
Han
H
H
Hui
A
A
Kohno
T
T
Manoukian
R
R
Whoriskey
J S
JS
Coccia
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000502:physiology; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018106:CD28 Antigens; D016207:Cytokines; C556692:ICOS protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands