ICOS Fc

Inducible T-cell costimulator (ICOS) is a T-cell-specific, surface receptor of the immunoglobulin superfamily that binds inducible costimulatory ligand (ICOSL), alternatively referred to as B7-H2, to play a critical role in the development and function of regulatory T-cells (Tregs) . ICOS joins CD28, CTLA-4 and PD-1 as a member of the growing CD28/CTLA-4 family of costimulatory immunoreceptors that function synergistically with members of the B7 family of transmembrane ligands, including B7-1, B7-2, B7-H1 (PD-L1), B7-H2 and PD-L2, to constitute crucial costimulatory pathways for T-cell and B-cell regulatory responses. As the main receptor of B7-H2, ICOS can have both negative and positive influence over immune response, including the direct downregulation of B7-H2, and is critically involved in the immunosuppression of tumor-associated memory CD4+ T-cells. Interaction between ICOS and B7-H2 on the surface of antigen presenting cells potentiates costimulatory signals responsible for enhancing basic T-cell response to foreign antigens, namely the augmentation of T-cell proliferation, the upregulation of molecules responsible for mediating intercellular interaction, and the secretion of cytokines such as IL-4, IL-10 and IL-21. The significant involvement of ICOS and B7-H2 interaction within an array of immunological responses, such as those of Th1, Th2 and Th17 cells, means that the blockade of this interaction has been linked to a number of autoimmune diseases, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), type 1 diabetes, and graft versus host disease (GVHD) . Unlike CD28, which is constitutively expressed on the surface of T-cells where it has restricted interaction with B7-H2, ICOS is expressed at low levels on naive T-cells and is upregulated on activated T-cells and regulatory T-cells (Tregs) after TCR ligation and CD28 stimulation. The CHO cell-derived Recombinant Human ICOS Fc is a glycosylated, homodimer 79.4 kDa of 706 amino acid residues whose monomer consists of the 120-amino-acid-length extracellular portion of ICOS fused to the 231-amino-acid-length Fc portion of human IgG1 by two glycines. The calculated molecular weight of Recombinant Human ICOS Fc dimer is 79.4 kDa; however, due to glycosylation, it migrates at an apparent molecular weight of approximately 40-45 kDa by SDS-PAGE analysis under reducing conditions.