Cutting Edge: Identification of GL50, a Novel B7-Like Protein That Functionally Binds to ICOS Receptor

Abstract

By the genetic selection of mouse cDNAs encoding secreted proteins, a B7-like cDNA clone termed mouse GL50 (mGL50) was isolated encoding a 322-aa polypeptide identical with B7h. Isolation of the human ortholog of this cDNA (hGL50) revealed a coding sequence of 309 aa residues with 42% sequence identity with mGL50. Northern analysis indicated GL50 to be present in many tissues including lymphoid, embryonic yolk sac, and fetal liver samples. Of the CD28, CTLA4, and ICOS fusion constructs tested, flow cytometric analysis demonstrated only mouse ICOS-IgG binding to mGL50 cell transfectants. Subsequent phenotyping demonstrated high levels of ICOS ligand staining on splenic CD19+ B cells and low levels on CD3+ T cells. These results indicate that GL50 is a specific ligand for the ICOS receptor and suggest that the GL50-ICOS interaction functions in lymphocyte costimulation.

ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+T cells

“…As revealed by mRNA expression studies, ICOS-L is expressed in lymphoid and nonlymphoid organs (3,7). B cells, T cells, and dendritic cells, which all have been shown to express ICOS-L on their cell surface, may account for ICOS-L expression in lymphoid organs; the cell type responsible for high-level expression of ICOS-L in nonlymphoid tissues, e.g., kidney, heart, or brain, has not been identified to date.…”

“…Two splice variants of human ICOS-L have been described and designated hGL50 (3) and B7-H2͞B7RP-1͞hLICOS (4)(5)(6). Both molecules have an identical extracellular domain but differ at the carboxyl-terminal end of their cytoplasmic regions.…”

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

“…IRBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] -immunized C57BL/6 mice were treated with anti-B7RP-1 mAb or control IgG from day -1 to day 7 for the induction phase or from day 8 to day 20 for the effector phase. The administration of anti-B7RP-1 mAb at the induction phase was not effective in terms of clinical ( Fig.…”

“…Unlike CD28, ICOS is not expressed on naive T cells, but induced after T cell activation [10][11][12]. Its ligand B7RP-1 (also known as B7 h, B7-H2, GL50, and LICOS) is constitutively expressed on B cells, macrophages, and dendritic cells [12][13][14][15][16]. Ligation of ICOS on activated T cells by mAb or B7RP-1 fusion protein enhanced cytokine production (IL-4, IL-5, IFN-c, and IL-10), whereas IL-2 production was not clearly enhanced [10,12,17].…”

Effects of ICOSLG expressed in mouse hematological neoplasm cell lines in the GVL reaction

“…Inducible co-stimulator (ICOS) is a relatively recently characterized member of the B7 family of immuneregulatory ligands, which is involved in the co-stimulation of T cells and is expressed only on activated T cells. [1][2][3] The first member of the B7 family, B7-1, was identified over 20 years ago and revealed to have co-stimulatory function when ligated to the CD28 receptor on T cells. [4][5][6][7] Several new members of the B7 family, such as B7-H1, ICOS ligand (LG), B7-H3 and B7-H4, have been identified since then.…”