Biolegend, 798804, Biotinylated Recombinant Human ICOS-Fc Chimera (carrier-free)

Inducible costimulatory molecule (ICOS) is a member of CD28 superfamily protein. It has unique roles in T cell activation and differentiation, splenic germinal center formation, and immunoglobulin class switching. The expression of ICOS within the first 48 hours after T cell activation suggests that it may contribute to the differentiation of T cells during the primary response. ICOS binds to its ligand B7H, which is constitutively expressed at low levels on the surface of APCs and is upregulated by TNF-α or lipopolysaccharide. It was demonstrated that ICOS-B7H2 interaction plays an important role in the generation of CD4+ and CD8+ Tregs, and mediates the suppressive functions of CD4+ Tregs by regulating CTLA-4 expression on cell surfaces induced by allogeneic CD40-activated B cells. In the ICOS-KO mice, the T cell-mediated isotype switching is impaired while the IFN-gamma response is slightly affected; in addition, the ICOS-negative T cells do not accumulate in B cell follicles. Also, secondary, but not primary, clonal proliferation of antigen-specific B cells is impaired in ICOS-KO mice, and therefore the generation of secondary antibody-secreting cells is also impaired. These results suggest that this protein plays a pivotal role in T cell activation and Th1/Th2 differentiation. Mouse and human B7-H2 exhibit cross species binding to ICOS. B7-H2 interaction costimulates T cell proliferation, development of B cells, plasma cells, follicular helper T cells, and germinal centers. In addition, human B7-H2 binds to CD28 and CTLA4. The interaction of human B7-H2 and CD28 can costimulate both human mouse naïve T cells and regulatory T cells (Treg). B7-H2 plays a role in the development of allergic asthma by enhancing Th2 biased immune responses, limiting Th17 responses, and promoting eosinophilic infiltration into the lungs. B7-H2 activation of ICOS on Tregs limits pulmonary inflammation and airway hyper-responsiveness, promotes the development of inhalational tolerance, and impairs anti-tumor immunity.